54 | id == 54
54 | category_id == 12
54 | category_order == 9
54 | category_name == Cardiovascular
54 | category_color == #C47AC0
54 | slug == heart-disease-NOS3
54 | title == Are You Genetically Vulnerable to Heart Disease (NOS3)?
54 | meta_description == NOS3 determines your risk of heart disease depending on your genetic variant. Find out where your genes stand.
54 | summary == <p><strong>Heart disease is one of the leading causes of death in the world. <em>NOS3</em> produces <em>nitric oxide</em> (NO), a key molecule that protects the function of your blood vessels. Read on to learn if your <em>NOS3</em> variant increases your risk of heart disease, and what you can do about it. </strong></p>
54 | overall_score_text == Heart Disease Score (based on NOS3 Gene)
54 | image == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/background/NOS3-Cardiovascular.jpg
54 | author_id == 12
54 | author_name == Carlos Tello
54 | author_title == PhD
54 | author_order == 55
54 | author_photo == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/author-photo/CarlosTello.webp
54 | author_intro == <p><strong>Carlos received his PhD and MS from the Universidad de Sevilla.</strong></p>    <p>Carlos spent 9 years in the laboratory investigating mineral transport in plants. He then started working as a freelancer, mainly in science writing, editing, and consulting. Carlos is passionate about learning the mechanisms behind biological processes and communicating science to both academic and non-academic audiences. He strongly believes that scientific literacy is crucial to maintain a healthy lifestyle and avoid falling for scams.</p>
54 | author_social_media_name == linkedin
54 | author_social_media_icon == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/social-icon/linkedin.png
54 | author_social_order == 1
54 | author_social_link == https://www.linkedin.com/in/carlos-tello-lacal-b946b4a7/
54 | reviewer_id == 1
54 | reviewer_name == Jasmine Foster
54 | reviewer_title == BSc, BEd
54 | medical_reviewer == None
54 | publish_date == 2019
54 | publish_date == 9
54 | publish_date == 26
54 | avg_rating == 5.0
54 | tags_id == 172
54 | tags_name == Blood Pressure
54 | tags_id == 137
54 | tags_name == Coronary Artery Disease
54 | tags_id == 135
54 | tags_name == Heart Attack
54 | tags_id == 134
54 | tags_name == Heart Disease
54 | tags_id == 173
54 | tags_name == NO
54 | tags_id == 174
54 | tags_name == NOS3 Gene
54 | permissions_favorite == False
54 | permissions_rate == False
54 | content_article == <h2><span style="font-weight: 400;">What Is the </span><em><span style="font-weight: 400;">NOS3 </span></em><span style="font-weight: 400;">Gene?</span></h2> <p><span style="font-weight: 400;">The </span><em><span style="font-weight: 400;">NOS3 </span></em><span style="font-weight: 400;">gene codes for a protein also called NOS3, short for </span><a href="../../gene/nos3/?utm_source=seo&amp;#38;utm_medium=selfhacked&amp;#38;utm_campaign=id00002"><span style="font-weight: 400;">nitric oxide synthase 3</span></a><span style="font-weight: 400;">. NOS3 is most abundant in the inner lining of the blood vessels, where it produces nitric oxide (NO) from the amino acid arginine [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/16585403"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/16416260"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">NO is a messenger molecule with multiple functions in the immune and nervous systems. Additionally, NOS3-derived NO increases blood flow and lowers the risk of heart disease [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6728140/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/21196271"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h3><span style="font-weight: 400;">Vessel Relaxation</span></h3> <p><span style="font-weight: 400;">In the blood vessels, NO activates a pathway that decreases the amount of free </span><a href="https://selfhacked.com/blog/calcium-101/"><span style="font-weight: 400;">calcium</span></a><span style="font-weight: 400;">. The low free calcium levels cause vessel relaxation [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/10320667/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964902/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Alternatively, NO breaks down the </span><a href="https://selfhacked.com/blog/oxidative-stress-101/"><span style="font-weight: 400;">free radical</span></a><span style="font-weight: 400;"> superoxide, both directly and by activating an antioxidant enzyme. By protecting the lining tissue from this molecule, it preserves its function and prevents vessel stiffness [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/14521592"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC300857/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">However, NO production must be tightly fine-tuned. Very high amounts may react with the superoxide anion and form the even more harmful peroxynitrite [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/24102471"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h3><span style="font-weight: 400;">Prevention of Clogged Arteries</span></h3> <p><span style="font-weight: 400;">NO diffuses across platelet membranes and increases cGMP levels in these cells. By doing so, it prevents platelets from being activated and clumping together inside the arteries [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1917966/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC39965/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Immune cells may bind to platelets and further increase the risk of artery-clogging. NO blocks the major inflammatory hub </span><a href="https://selfhacked.com/blog/nuclear-factor-kappa-b/"><span style="font-weight: 400;">NF-kB</span></a><span style="font-weight: 400;">, thus preventing </span><a href="https://selfhacked.com/blog/how-to-increase-and-decrease-white-blood-cells/"><span style="font-weight: 400;">white blood cells</span></a><span style="font-weight: 400;"> from attaching to the vessels and ending up bound to platelets [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/9895331"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC51723/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Some conditions are characterized by the overgrowth of smooth muscle cells in the vessels, which may contribute to artery-clogging. NO increases cGMP production, which blocks cell growth [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/7977701/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Alternatively, the antioxidant effect of NO reduces LDL damage by free radicals and prevents </span><a href="https://www.selfhacked.com/blog/cholesterol/"><span style="font-weight: 400;">cholesterol</span></a><span style="font-weight: 400;"> buildup in the vessels [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/15001455"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;"><span style="font-weight: 400;">The </span><em><span style="font-weight: 400;">NOS3 </span></em><span style="font-weight: 400;">gene is responsible for producing NO. This messenger molecule relaxes the blood vessels and prevents their clogging, thus increasing blood flow and protecting the heart.</span></span></p> <h2><span style="font-weight: 400;">Your NOS3 Results for Heart Disease</span></h2> <p>*3026001503664146*</p> <p><strong>Primary SNP: NOS3 rs1799983</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = Normal risk of heart disease</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = Increased blood pressure and risk of heart disease (especially coronary heart disease)</span></li> </ul> <p><span style="font-weight: 400;">Population Frequency:</span></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">Almost 70% of the world population has &lsquo;GG&rsquo;</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">In people with European ancestry, the frequency of the &lsquo;T&rsquo; allele is increased to 34%</span></li> </ul> <p><strong>Other Important SNPs:</strong></p> <p><strong>NOS3 rs2070744</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = Normal risk of heart disease</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = Increased risk of heart attack and coronary heart disease</span></li> </ul> <p><span style="font-weight: 400;">Population Frequency:</span></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">Approximately 60% of the world population have &lsquo;TT&rsquo;</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">The frequency of the &lsquo;TT&rsquo; genotype is reduced to 30% in European descendants</span></li> </ul> <p><strong>NOS3 rs3918226</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = Normal risk of heart disease</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = Increased risk and severity of heart and coronary disease</span></li> </ul> <p><span style="font-weight: 400;">Population Frequency:</span></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">94% of the world population have &lsquo;CC&rsquo;</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">17% of people with European ancestry have &lsquo;CT&rsquo; and only 1% have &lsquo;TT&rsquo;</span></li> </ul> <p>*9233535179424488*</p> <p><span style="font-weight: 400;">Among the different </span><em><span style="font-weight: 400;">NOS3 </span></em><span style="font-weight: 400;">polymorphisms, rs179983 has been most widely studied. In terms of heart function, it&rsquo;s preferable to have the &lsquo;GG&rsquo; genotype (as around 70% of the population does). The &lsquo;T&rsquo; variant produces a protein that can&rsquo;t reach its activation sites in cell membranes, ultimately decreasing NO production [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17449720"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The &lsquo;T&rsquo; allele was associated with an increased risk of coronary heart disease and heart attack in several studies. It&rsquo;s also more frequent in children with congenital heart disease and predicts a faster progression of heart damage in people with diabetes [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/30789045"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4856856/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/28865601"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/30140993"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">However, NO is a double-edged sword and the overproducing &lsquo;GG&rsquo; genotype may also have negative effects on the heart. It&rsquo;s associated with reduced heart function in people with kidney disease, increased risk of death in those with high blood pressure, and heart failure in African-Brazilians [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303420/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/27697448"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/20079452/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Another SNP, rs2070744, is also linked to heart attack and coronary heart disease. Almost 40% of people carry at least one copy of the &lsquo;C&rsquo; allele, which can be bound by a protein that blocks </span><em><span style="font-weight: 400;">NOS3 </span></em><span style="font-weight: 400;">production [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5317294/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/30789045"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/11063722/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Finally, the &lsquo;T&rsquo; allele of rs3918226 also results in lower NOS3 levels and is associated with a higher risk and severity of heart and coronary events. Fortunately, this allele is extremely rare and most people (81-99%) have the &lsquo;CC&rsquo; genotype [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/24019403/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/25102225"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3314599/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;"><span style="font-weight: 400;">Two </span><em><span style="font-weight: 400;">NOS3 </span></em><span style="font-weight: 400;">polymorphisms, rs179983 and rs2070744, are the main ones associated with heart and coronary disease. The minor allele of rs3918226 also increases the risk, but this mutation is very rare.</span></span></p> <h2><span style="font-weight: 400;">How Does </span><em><span style="font-weight: 400;">NOS3 </span></em><span style="font-weight: 400;">Affect Heart and Vessel Health?</span></h2> <p><span style="font-weight: 400;">*3026001503664146*</span></p> <h3><span style="font-weight: 400;">By Increasing Risk Factors</span></h3> <p><span style="font-weight: 400;">The &lsquo;T&rsquo; allele of rs179983 is a good predictor of high blood pressure, especially in Chinese populations. Nevertheless, some studies failed to find this association and suggested that factors such as the geographic origin or fat intake were much more influential [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/26994605"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3166328/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828038/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654571/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17762636"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/24846690"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">This allele is also linked to a higher risk of artery-clogging, probably because it increases vessel stiffness and blood cholesterol (both free and bound to </span><a href="https://www.selfhacked.com/blog/ldl-cholesterol/"><span style="font-weight: 400;">LDL</span></a><span style="font-weight: 400;">) [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749848/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17404185"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/31138610"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The minor &lsquo;C&rsquo; allele of rs2070744 was also associated with high blood pressure, possibly by reducing the levels of </span><a href="https://selfhacked.com/blog/adiponectin/"><span style="font-weight: 400;">adiponectin</span></a><span style="font-weight: 400;">, a protein that lowers blood pressure. Intriguingly, this allele increased vessel stiffness in Japanese women but not in men [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5683550/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/18230825/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907937/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Although rs179983 and rs2070744 are generally considered to predict an increased risk of high blood pressure during pregnancy (pre-eclampsia), not all studies found this association [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800677/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3217889/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/18463669"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Three studies on over 5,000 people associated the minor &lsquo;T&rsquo; allele at rs3918226 with increased blood pressure and artery stiffness [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3272453/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/24019403"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=rs3918226+stiffness"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h3><span style="font-weight: 400;">By Interfering with Medical Therapies</span></h3> <p><span style="font-weight: 400;">Your </span><em><span style="font-weight: 400;">NOS3 </span></em><span style="font-weight: 400;">variant may determine your risk of complications from medical procedures. Concretely, the minor allele of rs179983 increased the risk of coronary artery narrowing (restenosis), blood clot formation in the veins, and irregular </span><a href="https://www.selfhacked.com/blog/resting-heart-rate/"><span style="font-weight: 400;">heart rate</span></a><span style="font-weight: 400;"> after surgery [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4898353/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3724670/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4541653/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Variations in this gene may also reduce the effectiveness of conventional and alternative therapies. The minor &lsquo;T&rsquo; allele of rs3918226 predicted a worse response to the diuretic chlorthalidone in people with high blood pressure. Similarly, a treatment made from </span><a href="https://selfhacked.com/blog/salvia-miltiorrhiza-red-sage/"><span style="font-weight: 400;">red sage</span></a><span style="font-weight: 400;"> roots (salvianolate injection) was less effective in people with the &lsquo;T&rsquo; allele of rs179983 [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325375/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/24827774"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;"><span style="font-weight: 400;">The </span><em><span style="font-weight: 400;">NOS3 </span></em><span style="font-weight: 400;">polymorphisms mainly increase the risk of heart disease through their association with higher blood pressure, cholesterol levels, and artery stiffness. Some of them may also interfere with medical therapies.</span></span></p> <h2><span style="font-weight: 400;">How Can You Improve your </span><em><span style="font-weight: 400;">NOS3 </span></em><span style="font-weight: 400;">Phenotype?</span></h2> <p><span style="font-weight: 400;">There's many healthy lifestyle and diet approaches that can improve heart health, and also potentially counteract some the effects of NOS3.</span></p> <p>*3765434017328690*</p> <h3><span style="font-weight: 400;">Lifestyle</span></h3> <p><span style="font-weight: 400;">There are several lifestyle changes that may increase your NOS3 activity. These include:</span></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">Giving up smoking: cigarette smoke reduces NO production by activating the enzymes that compete with NOS3 for arginine (arginases). Smokers are at greater risk of heart disease and more so if they also have </span><em><span style="font-weight: 400;">NOS3 </span></em><span style="font-weight: 400;">risk alleles [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4391310/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1978174/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/25304051"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Avoiding pollution: environmental pollutants reduce both NOS3 production and NO release while increasing free radicals. Living in heavily polluted areas increases the risk of heart disease [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/8890937/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161281/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Exercising more: exercise reduces blood pressure by stimulating NOS3 activity and NO release. Additionally, regular exercise protects from heart disease [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/24748593"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/25129643"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172294/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></li> </ul> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Research shows that giving up smoking, exercising, and reducing exposure to pollution can significantly improve NOS3 function and protect the heart.</span></p> <h3><span style="font-weight: 400;">Diet</span></h3> <p><span style="font-weight: 400;">Research has revealed the beneficial effects of two types of dietary fatty acids, especially for people with the minor &lsquo;T&rsquo; allele at&nbsp; rs1799983:</span></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">Omega-3: these fatty acids are found in </span><a href="http://selfhacked.com/blog/top-22-science-based-health-benefits-of-fish-oil/"><span style="font-weight: 400;">fish oil</span></a><span style="font-weight: 400;"> and linked to heart health. One of them (</span><a href="http://selfhacked.com/blog/top-22-science-based-health-benefits-of-fish-oil/"><span style="font-weight: 400;">DHA</span></a><span style="font-weight: 400;">) prevents the cytokine </span><a href="http://selfhacked.com/blog/supplements-lifestyle-factors-influence-tnf-interleukin-6-il-6/"><span style="font-weight: 400;">TNF-alpha</span></a><span style="font-weight: 400;"> from blocking NOS3 production [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/26802937"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/20409549"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013782/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Monounsaturated: </span><a href="https://selfhacked.com/blog/olive-oil/"><span style="font-weight: 400;">olive oil</span></a><span style="font-weight: 400;">, rich in the monounsaturated </span><a href="https://selfhacked.com/blog/oleic-acid-benefits/"><span style="font-weight: 400;">oleic acid</span></a><span style="font-weight: 400;">, is strongly associated with a reduced risk of heart disease [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4030221/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/26994605"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></li> </ul> <p><span style="font-weight: 400;">Conversely, saturated fats may further reduce NOS3 production and increase the risk of heart disease in people with risk variants [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/26994605"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">One of the mechanisms by which antioxidants reduce the generation of free radicals is by increasing NOS3 production. People with the rs2070744-C or rs3918226-T mutant variants may benefit from including the following antioxidants in their diets [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/12512693"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2913633/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]:</span></p> <ul> <li style="font-weight: 400;"><a href="https://selfhacked.com/blog/top-15-scientific-health-benefits-of-resveratrol-with-references/"><span style="font-weight: 400;">Resveratrol</span></a><span style="font-weight: 400;"> (found in grapes, </span><a href="https://selfhacked.com/blog/blueberries-health-benefits/"><span style="font-weight: 400;">blueberries</span></a><span style="font-weight: 400;">, peanuts, pistachios, and dark chocolate)</span></li> <li style="font-weight: 400;"><a href="https://www.selfhacked.com/blog/green-tea/"><span style="font-weight: 400;">Epigallocatechin</span></a><span style="font-weight: 400;"> gallate (mainly in </span><a href="http://selfhacked.com/blog/green-tea/"><span style="font-weight: 400;">green tea</span></a><span style="font-weight: 400;">)</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Genistein (in soybeans, broad beans, and lupins)</span></li> <li style="font-weight: 400;"><a href="https://www.selfhacked.com/blog/chlorogenic-acid/"><span style="font-weight: 400;">Chlorogenic acid</span></a><span style="font-weight: 400;"> (in coffee and tea)</span></li> <li style="font-weight: 400;"><a href="https://www.selfhacked.com/blog/quercetin-22-scientifically-proven-benefits-quercetin/"><span style="font-weight: 400;">Quercetin</span></a><span style="font-weight: 400;"> (in leafy vegetables, broccoli, apples, peppers, tea, and fruit juices)</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Kaempferol (in apples, grapes, tomatoes, green tea, and potatoes)</span></li> <li style="font-weight: 400;"><a href="https://www.selfhacked.com/blog/rutin/"><span style="font-weight: 400;">Rutin</span></a><span style="font-weight: 400;"> (in oranges, buckwheat, apricots, cherries, grapes, and plums)</span></li> </ul> <p><span style="font-weight: 400;">However, the benefits of these antioxidants for NOS3 function have mainly been tested in animals and cells. Their effects may not be the same in humans.</span></p> <p><span style="font-weight: 400;">Iron is a cofactor required for NOS3 to function. Because excessive doses may </span><em><span style="font-weight: 400;">increase </span></em><span style="font-weight: 400;">the risk of coronary artery disease, it&rsquo;s preferable to obtain it from iron-rich foods such as shellfish, liver, sardines, lentils, and spinaches than from supplements [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/23276910"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3927548/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In turn, sodium-rich diets are strongly linked to high blood pressure and risk of heart disease. Reducing </span><a href="https://selfhacked.com/blog/is-salt-good-or-bad-the-science-on-the-health-effects-of-salt/"><span style="font-weight: 400;">salt</span></a><span style="font-weight: 400;"> intake may be especially beneficial in people with variants that increase blood pressure such as rs1799983-T [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478144/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Foods rich in omega-3 or monounsaturated fatty acids, antioxidants, and iron can increase the activity of NOS3 and its heart-protecting effects. In turn, it&rsquo;s better to avoid saturated fats and sodium.</span></p> <h3><span style="font-weight: 400;">Supplements</span></h3> <p><span style="font-weight: 400;">Tetrahydrobiopterin (</span><a href="https://selfhacked.com/blog/tetrahydrobiopterin-bh4-role-body-buy/"><span style="font-weight: 400;">BH4</span></a><span style="font-weight: 400;">) is an essential molecule for NOS3 function. People with underactive NOS3 variants may benefit from taking BH4 or supplements that increase its availability such as </span><a href="https://selfhacked.com/blog/16-proven-benefits-vitamin-b9-folate-folic-acid/"><span style="font-weight: 400;">methylfolate</span></a><span style="font-weight: 400;"> and </span><a href="https://selfhacked.com/blog/need-know-vitamin-c-32-science-based-health-benefits/"><span style="font-weight: 400;">vitamin C</span></a><span style="font-weight: 400;"> [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/16585403"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3213424/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/10850963"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/11243424"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><a href="https://selfhacked.com/blog/5-natural-ace-inhibitors-with-clinical-trials/"><span style="font-weight: 400;">Substances with ACE inhibitory activity</span></a><span style="font-weight: 400;"> are particularly beneficial to those with mutated </span><em><span style="font-weight: 400;">NOS3 </span></em><span style="font-weight: 400;">variants because they lower blood pressure and increase NOS3 production. They include </span><a href="https://selfhacked.com/blog/garlic-health-benefits/"><span style="font-weight: 400;">garlic</span></a><span style="font-weight: 400;">, </span><a href="https://selfhacked.com/blog/whey-protein-health-benefits/"><span style="font-weight: 400;">whey protein</span></a><span style="font-weight: 400;">, </span><a href="https://selfhacked.com/blog/pycnogenol-pine-bark-extract-health-benefits/"><span style="font-weight: 400;">pycnogenol</span></a><span style="font-weight: 400;">, and </span><a href="https://selfhacked.com/blog/pomegranate/"><span style="font-weight: 400;">pomegranate</span></a><span style="font-weight: 400;"> [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/25837272"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/29087242"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6077626/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/27888156"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Additionally, people with risk NOS3 variants may benefit from supplements that protect from heart disease by reducing blood pressure, fat levels, and artery stiffness, such as </span><a href="https://selfhacked.com/blog/ubiquinol-benefits/"><span style="font-weight: 400;">ubiquinol</span></a><span style="font-weight: 400;">, bergamot oil, </span><a href="https://selfhacked.com/blog/l-arginine/"><span style="font-weight: 400;">arginine</span></a><span style="font-weight: 400;">, and red yeast rice [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17287847"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/19572741"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/22137067"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/18549841"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">As was the case for foods, many studies have only been carried out in animals or cells and their results may not apply to humans.</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Supplements increasing the levels or availability of the molecules required by NOS3 to function may help protect the heart. Those lowering blood pressure may help in some cases.</span></p> <h3><span style="font-weight: 400;">Drugs</span></h3> <p><span style="font-weight: 400;">In addition to blocking cholesterol production, statins increase NOS3 levels and activity. As a result, they may compensate for mutations that reduce the production of this protein. This is particularly the case in people with the &lsquo;CC&rsquo; genotype at rs2070744 [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/15864134/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/16962929/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/16938300/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/23876348/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">ACE blockers lower blood pressure by reducing the activity of the hormone </span><a href="../../gene/AGTR1/?utm_source=seo&amp;#38;utm_medium=selfhacked&amp;#38;utm_campaign=id00002"><span style="font-weight: 400;">angiotensin II</span></a><span style="font-weight: 400;"> and increasing NOS3 production. Polymorphisms with reduced NOS3 production are associated with a better response to the ACE blocker enalapril [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/22706620/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/27060232"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Similarly, the minor alleles of both rs1799983 and rs2070744 predicted a better response to the angiotensin II receptor blocker olmesartan [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394138/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In some cases, a NOS3 polymorphism may determine which drug from the same class to choose. In a study of over 30,000 people, those with the &lsquo;T&rsquo; variant of rs1799983 taking the calcium blocker amlodipine had lower risk of stroke than those on </span><a href="https://www.selfhacked.com/blog/lisinopril/"><span style="font-weight: 400;">lisinopril</span></a><span style="font-weight: 400;"> [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3314599/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Consult with your doctor before taking any drugs or making any changes in your treatment, especially if you have a diagnosed heart condition.</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;"><span style="font-weight: 400;">Your </span><em><span style="font-weight: 400;">NOS3 </span></em><span style="font-weight: 400;">variant may determine which drugs for heart conditions work best for you.</span></span></p>
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54 | content_learn_more_3026001503664146_text == Based on the variants we looked at, your NOS3 gene makes you somewhat more likely to develop heart disease. However, this doesn't necessarily reflect your overall risk of heart disease, just one gene related to it. Exercise healthy fats, antioxidant foods, and supplements may help. Keep scrolling to find out more.
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rsIDs = rs3918226,rs179983,rs2070744,rs1799983
rsStatus = rs3918226,NOS3,chr7,150993088,C,T,,,21,16,HET
rsStatus = rs179983,ATXN1,chr6,16349913,A,G,,,30,0,Normal
rsStatus = rs2070744,NOS3,chr7,150992991,C,G,T,,36,0,Normal
rsStatus = rs1799983,NOS3,chr7,150999023,T,A,G,,31,0,Normal
