236 | id == 236
236 | category_id == 18
236 | category_order == 15
236 | category_name == Weight
236 | category_color == #C47AC0
236 | slug == CDKAL1-weight
236 | title == Can This Gene Protect You From Obesity (CDKAL1)?
236 | meta_description == CDKAL1 encodes a protein involved in insulin production. Learn about its variants associated with BMI and diabetes here.
236 | summary == <p style="text-align:justify"><strong>The CDKAL1 gene encodes a protein that stimulates the production and release of insulin. Gene variants with possibly reduced activity are associated with reduced BMI but increased diabetes risk. Read on to learn more.</strong></p>
236 | overall_score_text == Your Weight Score (Based on CDKAL1 Gene)
236 | image == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/background/CDKAL1--Weight.jpg
236 | author_id == 12
236 | author_name == Carlos Tello
236 | author_title == PhD
236 | author_order == 55
236 | author_photo == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/author-photo/CarlosTello.webp
236 | 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>
236 | author_social_media_name == linkedin
236 | author_social_media_icon == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/social-icon/linkedin.png
236 | author_social_order == 1
236 | author_social_link == https://www.linkedin.com/in/carlos-tello-lacal-b946b4a7/
236 | reviewer == None
236 | medical_reviewer_id == 11
236 | medical_reviewer_name == Puya Yazdi
236 | medical_reviewer_title == MD
236 | publish_date == 2020
236 | publish_date == 7
236 | publish_date == 10
236 | avg_rating == 5.0
236 | tags_id == 186
236 | tags_name == BMI
236 | tags_id == 462
236 | tags_name == Body Fat
236 | tags_id == 530
236 | tags_name == CDKA Gene
236 | tags_id == 127
236 | tags_name == Diabetes Type 2
236 | tags_id == 139
236 | tags_name == Insulin
236 | tags_id == 165
236 | tags_name == Obesity
236 | permissions_favorite == False
236 | permissions_rate == False
236 | content_article == <p><em><span style="font-weight: 400;">This article is for informational purposes only. None of the information here should be taken as medical advice. If you are struggling to maintain a healthy weight, seek medical help. </span></em><em><span style="font-weight: 400;">Keep in mind that these results are based on association studies, which are correlative and aren&rsquo;t necessarily causative. Any single genetic variant will typically contribute only a small proportion to the overall risk of the condition, and non-genetic factors play a large role in developing a condition as well. Therefore, just because you have one of these genotypes does not necessarily mean you are at an increased risk of developing this condition!</span></em></p> <h2><strong>What Is the <em>CDKAL1 </em>Gene?</strong></h2> <p><span style="font-weight: 400;">The </span><a href="../../../gene/cdkal1/"><em><span style="font-weight: 400;">CDKAL1 </span></em><span style="font-weight: 400;">gene</span></a><span style="font-weight: 400;"> encodes the &lsquo;</span><em><span style="font-weight: 400;">CDK5 regulatory subunit-associated protein 1-like 1</span></em><span style="font-weight: 400;">&rsquo; protein, so called because it&rsquo;s very similar to the regulatory subunit of CDK5 [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3516729/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p><span style="font-weight: 400;">CDK5 is a messenger protein with multiple functions, including the inhibition of </span><a href="https://selfhacked.com/blog/insulin-101/"><span style="font-weight: 400;">insulin</span></a><span style="font-weight: 400;"> production in the pancreas. The regulator protein similar to CDKAL1 (</span><a href="../../../gene/cdk5rap1/"><span style="font-weight: 400;">CDK5RAP1</span></a><span style="font-weight: 400;">) blocks CDK5 activation and allows insulin production, thus preventing the development of type 2 diabetes from excess sugar [</span><a href="https://pubmed.ncbi.nlm.nih.gov/16155576"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/16887799/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/11882646/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><em><span style="font-weight: 400;">CDKAL1 </span></em><span style="font-weight: 400;">is highly expressed in the muscles, brain, and pancreas. The CDKAL1 protein activates the expression of the proinsulin gene and mice lacking </span><em><span style="font-weight: 400;">CDKAL1 </span></em><span style="font-weight: 400;">had reduced insulin production and secretion in response to </span><a href="https://selfhacked.com/blog/glucose/"><span style="font-weight: 400;">glucose</span></a><span style="font-weight: 400;">. In line with this, </span><em><span style="font-weight: 400;">CDKAL1 </span></em><span style="font-weight: 400;">variants have been associated with reduced pancreatic function and higher diabetes risk [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067665/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3516729/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3500257/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3000340/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/21908934/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/17804762/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/20568056/"><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;">The <em>CDKAL1 </em>gene encodes a protein similar to CDK5RAP1 and involved in insulin production and secretion.</span></p> <h2><strong><em>CDKAL1 </em>Variants in Body Weight</strong></h2> <p><span style="font-weight: 400;">The major &lsquo;C&rsquo; variant of </span><a href="../../../snp/rs2206734/"><span style="font-weight: 400;">rs2206734</span></a><span style="font-weight: 400;"> has been associated with increased BMI and obesity rates in East Asian and Canadian adults, as well as in Chinese children. Conversely, this variant protected East Asian adults and Greek children from type 2 diabetes and </span><a href="https://www.selfhacked.com/blog/top-tips-for-fixing-insulin-resistance/"><span style="font-weight: 400;">insulin resistance</span></a><span style="font-weight: 400;"> [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3838874/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/26717541/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4724138/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/32312375/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/29444352/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3973700/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Another major variant, &lsquo;T&rsquo; at </span><a href="../../../snp/rs9356744/"><span style="font-weight: 400;">rs9356744</span></a><span style="font-weight: 400;">, has also been associated with increased BMI in East Asians. Again, this allele reduced the risk of developing type 2 diabetes in Chinese adults and insulin resistance in Greek children [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3288728/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/29933462/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3973700/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The major &lsquo;A&rsquo; variant of </span><a href="../../../snp/rs4712523/"><span style="font-weight: 400;">rs4712523</span></a><span style="font-weight: 400;"> was also associated with increased BMI in Japanese and reduced risk of type 2 diabetes in Chinese populations [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3500257/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/22437209/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/31639799/"><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; variant of </span><a href="../../../snp/rs7754840/"><span style="font-weight: 400;">rs7754840</span></a><span style="font-weight: 400;"> is most well-known for its association with increased risk of gestational and type 2 diabetes, reduced insulin secretion, and better response to antidiabetic treatment. Chinese carriers of the &lsquo;C&rsquo; variant had higher waist circumference and waist-to-hip ratio, but a Dutch study found this allele unrelated to BMI [</span><a href="https://pubmed.ncbi.nlm.nih.gov/30074065/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694230/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/18285412/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854407/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106578/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2796390/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The </span><a href="../../../snp/rs7756992/"><span style="font-weight: 400;">rs7756992</span></a><span style="font-weight: 400;"> polymorphism has also been most widely investigated concerning its link to diabetes. In addition to increased risk of type 2 and gestational diabetes, its minor &lsquo;G&rsquo; variant is associated with leanness in diabetics and reduced birth weight [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3816287/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/30074065/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907669/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2750235/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/20490451/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4717941/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h3><strong>How It Works</strong></h3> <p><span style="font-weight: 400;">Although none of the studies tested the effects of the variants on </span><em><span style="font-weight: 400;">CDKAL1 </span></em><span style="font-weight: 400;">expression or activity, some risk alleles for diabetes have been shown to reduce insulin production and secretion. Based on the general mechanism of the protein, we can speculate that variants associated with diabetes have a reduced CDKAL1 activity [</span><a href="https://pubmed.ncbi.nlm.nih.gov/18264689/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/26119585/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In most cases, there was an association between reduced risk of diabetes and increased BMI. Insulin reduces blood glucose levels by promoting its uptake into the cells. Variants reducing its production may cause diabetes because the excess of blood sugar damages the pancreas. Alternatively, they may reduce weight gain by preventing sugar from being transformed into storage fats in the cells [</span><a href="https://pubmed.ncbi.nlm.nih.gov/25515340/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/28074888/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Notably, the minor variant of rs7754840 was associated with both diabetes and increased belly fat in Chinese. The fact that this polymorphism had no effect on BMI in a Dutch study suggests that its effect is probably dependent on the ethnicity. Moreover, the different </span><em><span style="font-weight: 400;">CDKAL1 </span></em><span style="font-weight: 400;">variants are often inherited together and could influence the overall effects observed [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106578/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2796390/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">However, the effects of the different variants may be partly counteracted by the activity of CDKAL1 on fatty tissues. Studies in engineered mice showed that CDKAL1 blocks the development of fat cells and promotes calorie-burning by brown fat [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5544666/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641635/"><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;"><em>CDKAL1 </em>variants with reduced activity and insulin production are generally associated with both increased diabetes risk and reduced BMI.</span></p> <h2><strong>Your <em>CDKAL1 </em>Results for Body Weight</strong></h2> <p>*2404386043691071*</p> <p>&nbsp;</p> <h3><strong>SNP Summary and Table</strong></h3> <p><strong>Primary SNP:</strong></p> <p><strong><em>CDKAL1 </em></strong><strong>rs2206734</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = associated with increased BMI and obesity rates. Reduced risk of type 2 diabetes.</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = associated with reduced BMI and obesity rates. Increased risk of type 2 diabetes.</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">56% of the world population carries two copies of the major &lsquo;C&rsquo; allele.</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">The &lsquo;T&rsquo; variant is especially rare in European descendants (only 4% of &lsquo;TT&rsquo;).</span></li> </ul> <p><strong>Other Important SNPs:</strong></p> <p><strong><em>CDKAL1 </em></strong><strong>rs9356744&nbsp;</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = associated with increased obesity rates. Reduced risk of type 2 diabetes.</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = associated with reduced obesity rates. Increased risk of type 2 diabetes.</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">The &lsquo;C&rsquo; variant is only slightly less common than &lsquo;T&rsquo; and the most common situation is to carry one copy of each one.</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">The &lsquo;C&rsquo; variant is least common in people of European ancestry (only 8% of &lsquo;CC&rsquo;).</span></li> </ul> <p><strong><em>CDKAL1 </em></strong><strong>rs4712523</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;A&rsquo; = associated with increased obesity rates. Reduced risk of type 2 diabetes.</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = associated with reduced obesity rates. Increased risk of type 2 diabetes.</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">The genotype distribution is very similar to that of rs9356744 for all ethnicities.</span></li> </ul> <p><strong><em>CDKAL1 </em></strong><strong>rs7754840&nbsp;</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = not associated with obesity or diabetes.</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = associated with increased risk of type 2 and gestational diabetes. Higher waist circumference and waist-to-hip ratio in Chinese.</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">The genotype distribution is very similar to that of rs9356744 and rs4712523 for all ethnicities.</span></li> </ul> <p><strong><em>CDKAL1 </em></strong><strong>rs7756992&nbsp;</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;A&rsquo; = not associated with obesity or diabetes.</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = associated with increased risk of type 2 and gestational diabetes. Reduced weight in diabetics and newborns.</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">The &lsquo;G&rsquo; variant is only slightly less common than &lsquo;A&rsquo; and the most common situation is to carry one copy of each one.</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">The &lsquo;A&rsquo; variant is most common in European and South Asian descendants.</span></li> </ul> <p>*1483409256095380*</p> <p>&nbsp;</p> <h2><strong>Recommendations to Improve Weight Control</strong></h2> <p><em><span style="font-weight: 400;">You may try the complementary approaches listed below if you and your doctor determine that they could be appropriate for you. Discuss the strategies listed here with your doctor. Remember that none of them should ever be done in place of what your doctor recommends or prescribes.</span></em></p> <p>*7203620961007309*</p> <p>&nbsp;</p> <h3><strong>Diet</strong></h3> <h4><strong>Low-Saturated Fat Diets</strong></h4> <p><span style="font-weight: 400;">In a study in mice, those lacking </span><em><span style="font-weight: 400;">CDKAL1 </span></em><span style="font-weight: 400;">gained less weight from a </span><a href="http://selfhacked.com/blog/low-carb-diet-vs-high-carb-diet/"><span style="font-weight: 400;">high-fat diet</span></a><span style="font-weight: 400;">. This suggests that carriers of variants with presumably increased CDKAL1 activity (such as the major alleles of rs2206734, rs9356744, and rs4712523) should be especially mindful of their fat intake [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3500257/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Several meta-analyses have associated low-fat diets with significant and sustained </span><a href="http://selfhacked.com/blog/a-comprehensive-list-of-effective-ways-to-lose-weight/"><span style="font-weight: 400;">weight loss</span></a><span style="font-weight: 400;">, as well as with reduced weight gain. Omega 3's and MUFAs from </span><a href="https://selfhacked.com/blog/olive-oil/"><span style="font-weight: 400;">olive oil</span></a><span style="font-weight: 400;"> are very healthy, so it would be wisest to cut down mainly on </span><em><span style="font-weight: 400;">saturated </span></em><span style="font-weight: 400;">fat [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667723/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3516671/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/10889789"><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;">Eating a diet low in saturated fats helps lose weight. People with risk <em>CDKAL1 </em>variants should be especially mindful of the amount of fats in their diet.</span></p>
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236 | content_learn_more_1483409256095380_text == Based on the variants we looked at, your CDKAL1 gene is associated with slightly higher obesity rates. However, this doesn't necessarily reflect your overall risk, just one gene related to it. Eat a diet low in saturated fats to maintain a healthy weight. Keep reading to find out more.
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rsIDs = rs9356744,rs7754840,rs4712523,rs7756992,rs2206734
rsStatus = rs9356744,CDKAL1,chr6,20685255,T,C,,,14,7,HET
rsStatus = rs7754840,CDKAL1,chr6,20661019,G,A,C,T,23,0,Normal
rsStatus = rs4712523,CDKAL1,chr6,20657333,A,G,T,,19,13,HET
rsStatus = rs7756992,CDKAL1,chr6,20679478,A,G,T,,10,12,HET
rsStatus = rs2206734,CDKAL1,chr6,20694653,C,G,T,,23,0,Normal
