91 | id == 91
91 | category_id == 6
91 | category_order == 4
91 | category_name == Thyroid
91 | category_color == #C47AC0
91 | slug == FCRL3-thyroid-autoimmunity-Graves
91 | title == The Missing Link Between Immunity and Thyroid Disorders (FCRL3)
91 | meta_description == FCRL3 has complex roles in immune system regulation. Click to learn about its variants associated with thyroid autoimmunity.
91 | summary == <p style="text-align:justify"><strong>The FCRL3 gene encodes for a protein with complex roles in immune system regulation. Scientists have found surprising links between specific FCRL3 variants and thyroid autoimmunity.</strong></p>
91 | overall_score_text == Your Graves’ disease score (based on FCRL3)
91 | image == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/background/FCRL3--Thyroid.jpg
91 | author_id == 9
91 | author_name == Aleksa Ristic
91 | author_title == MS (Pharmacy)
91 | author_order == 45
91 | author_photo == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/author-photo/Aleksa.jpg
91 | author_intro == <p><strong>Aleksa received his MS in Pharmacy from the University of Belgrade, his master thesis focusing on protein sources in plant-based diets.</strong>&nbsp;&nbsp;</p>    <p>Aleksa is passionate about herbal pharmacy, nutrition, and functional medicine. He found a way to merge his two biggest passions&mdash;writing and health&mdash;and use them for noble purposes. His mission is to bridge the gap between science and everyday life, helping readers improve their health and feel better.</p>
91 | reviewer == None
91 | medical_reviewer_id == 11
91 | medical_reviewer_name == Puya Yazdi
91 | medical_reviewer_title == MD
91 | publish_date == 2020
91 | publish_date == 2
91 | publish_date == 5
91 | avg_rating == 5.0
91 | tags_id == 33
91 | tags_name == Autoimmunity
91 | tags_id == 242
91 | tags_name == B cells
91 | tags_id == 96
91 | tags_name == Cytokines
91 | tags_id == 244
91 | tags_name == Fish oil
91 | tags_id == 83
91 | tags_name == Grave's Disease
91 | tags_id == 95
91 | tags_name == Immune System
91 | tags_id == 243
91 | tags_name == Smoking
91 | tags_id == 245
91 | tags_name == Sunlight
91 | tags_id == 41
91 | tags_name == Thyroid
91 | tags_id == 104
91 | tags_name == Tregs
91 | permissions_favorite == False
91 | permissions_rate == False
91 | content_article == <table style="width: 90%; border-collapse: collapse; margin-left: auto; margin-right: auto;" border="1" cellpadding="10"> <tbody> <tr> <td style="width: 100%;"><strong>Note:</strong>&nbsp;The&nbsp;<em>FCRL3</em>&nbsp;gene is one of the genes we analyze in our&nbsp;<a href="https://get.selfdecode.com/gene-reports/inflammation/"><em>Inflammation DNA Wellness Report</em></a>, along with many other genes. If you're looking for a comprehensive report on inflammation-related genes, check it out!</td> </tr> </tbody> </table> <p>&nbsp;</p> <h2><strong>What is FCRL3?</strong></h2> <p><em><span style="font-weight: 400;">Synonyms</span></em><span style="font-weight: 400;">: CD307c, FCRH3, IFGP3, IRTA3, SPAP2</span></p> <p><a href="../../gene/fcrl3/"><span style="font-weight: 400;">FCRL3</span></a><span style="font-weight: 400;"> (Fc receptor-like 3) gene encodes for a receptor with complex roles in the immune system. It can send both inhibitory and stimulatory signals to immune cells upon activation, enabling it to modulate the body&rsquo;s response to infectious agents and other threats [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/11929751/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17201682/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">As its full name suggests, FCRL3 resembles Fc receptors on immunoglobulin (antibody) chains. Despite recent progress in understanding, scientists are still exploring its exact roles in immunity [</span><a href="https://www.ncbi.nlm.nih.gov/gene/115352"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/gene?Db=gene&amp;Cmd=DetailsSearch&amp;Term=115352"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Both B-cells and T-cells express FCRL3 receptors, which mediate their communication and development. Unfortunately, like many other genes involved in immune response, FCRL3 has a dark side&mdash;certain variations may impair its function and correlate with autoimmunity [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/20933010/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17462505"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">FCRL3 encodes for a receptor that can both suppress and stimulate immune cells, but its exact role remains unknown. Specific variants in this gene have been associated with autoimmunity.</span></p> <h2><strong>FCRL3 Variants and Thyroid Autoimmunity</strong></h2> <p><span style="font-weight: 400;">Back in 2005, a group of Japanese authors investigated the connection between the SNPs in FCRL3 and different autoimmune conditions. According to their results, the "G" allele at </span><a href="../../snp/rs7528684/"><span style="font-weight: 400;">rs7528684</span></a><span style="font-weight: 400;"> correlates with thyroid autoimmunity&mdash;particularly </span><a href="https://selfhacked.com/blog/graves-disease/"><span style="font-weight: 400;">Graves' disease</span></a><span style="font-weight: 400;"> [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1362949/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The study provided valuable insights into the mechanisms behind FCRL3-associated autoimmunity, which we&rsquo;ll discuss later.</span></p> <p><span style="font-weight: 400;">A clinical trial of nearly 2,000 UK subjects confirmed the link between rs7528684-G and Graves&rsquo; disease (GD) in Europeans. Carriers of this allele had 17% higher GD rates. Another FCRL3 variant, </span><a href="../../snp/rs3761959/"><span style="font-weight: 400;">rs3761959</span></a><span style="font-weight: 400;">-T, showed an even stronger association and correlated with 20% higher disease rates [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/16384851/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In 2,500 people of European ancestry, scientists identified another SNP associated with Graves&rsquo; disease: people with the &ldquo;C&rdquo; allele at </span><a href="../../snp/rs7522061/"><span style="font-weight: 400;">rs7522061</span></a><span style="font-weight: 400;"> had 25% higher GD incidence. According to the study, rs7522061 is a &ldquo;twin&rdquo; SNP of rs3761959 rather than a separate factor [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2680141/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Two Chinese studies of 20,000 total participants came to similar conclusions for two primary SNPs: rs3761959-T and rs7528684-G correlated with 22-23% higher rates of Graves' disease [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/21841780/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3591391/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The above variations also correlated with Graves' ophthalmopathy (GO), a complication that attacks the eyes, in another Chinese study of 1,200 people [</span><a href="https://europepmc.org/article/PMC/4659137"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In different populations across the globe, they&rsquo;ve been associated with other autoimmune conditions, such as [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/24117236"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1954681/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/18313765"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]:</span></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">Rheumatoid arthritis</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Lupus</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Type 1 diabetes</span></li> <li style="font-weight: 400;"><a href="https://selfhacked.com/blog/causes-symptoms-diagnosis-risk-factors-of-multiple-sclerosis/"><span style="font-weight: 400;">Multiple sclerosis</span></a></li> </ul> <p><span style="font-weight: 400;">However, it&rsquo;s important to note that the risk/beneficial alleles are not the same for each disease. In other words, those with a specific FCRL3 variant can be prone to one condition but protected against another.</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Three FCRL3 variants &mdash;rs7528684, rs3761959, and rs7522061&mdash; correlate with Graves&rsquo; disease and other autoimmune conditions in European and Asian populations.</span></p> <h3><strong>How It Works</strong></h3> <p><span style="font-weight: 400;">The SNPs discussed above belong to a &ldquo;block&rdquo; of four variations that are almost always inherited together. In other words, they act as a single genetic factor.</span></p> <p><span style="font-weight: 400;">After detailed experiments, scientists concluded that rs7528684 is likely a functional SNP driving the connection with Graves&rsquo; disease. The &ldquo;G&rdquo; allele increases FCRL3 expression by enhancing its interaction with </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;">, a major inflammatory transcription factor [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1362949/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3591391/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Increased FCRL3 expression causes B-cells to &ldquo;break the tolerance&rdquo; &mdash; it allows the survival of self-attacking B-cells that create antibodies to healthy thyroid structures, such as the </span><a href="https://www.selfhacked.com/blog/thyroid-stimulating-hormone/"><span style="font-weight: 400;">TSH</span></a><span style="font-weight: 400;"> receptor [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/20933010/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/19843936/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h4><strong>The Role of Tregs</strong></h4> <p><a href="http://selfhacked.com/blog/treg/"><span style="font-weight: 400;">Regulatory T cells</span></a><span style="font-weight: 400;"> (Tregs) play a central role in suppressing an overactive immune response. Surprisingly, Tregs with FCRL3 on their surface have a reduced ability to inhibit T cells. This phenomenon lowers immune tolerance and opens the door to autoimmunity [</span><a href="https://ghr.nlm.nih.gov/gene/FCRL3"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2894810/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2894810/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Scientists are still investigating if other SNPs in this block have separate functional roles that impact the immune system regulation.</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">The &ldquo;G&rdquo; allele at rs7528684 increases FCRL3 expression by allowing NF-kB to bind. This may contribute to autoimmunity by reducing B-cell tolerance and suppressing regulatory T cells.</span></p> <h2><strong>Your FCRL3 Results for Graves&rsquo; Disease</strong></h2> <p><strong><em><span style="font-weight: 400;">You can see your genotype for key FCRL3</span><span style="font-weight: 400;"> SNPs in the table below. However, keep in mind that these results are based on association studies, and more research will be needed to know what role (if any) these variants play in actually </span><span style="font-weight: 400;">causing</span><span style="font-weight: 400;"> thyroid disorders. Also, many different factors &mdash; including other genetic and environmental factors &mdash; can influence thyroid health. Therefore, just because you have one of these genotypes does not necessarily mean you are at an increased risk of developing a thyroid disorder!</span></em></strong></p> <h3><strong>SNP Table</strong></h3> <p><strong>*1726778945325757*</strong></p> <h3><strong>SNP Summary</strong></h3> <p><strong>Primary SNP:</strong></p> <p><strong><em>FCRL3</em></strong> <a href="../../snp/rs7528684/"><strong>rs7528684</strong></a><span style="font-weight: 400;">:</span></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&ldquo;G&rdquo; - correlates with Graves&rsquo; disease</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&ldquo;A&rdquo; - doesn&rsquo;t correlate with Graves&rsquo; disease</span></li> </ul> <p><strong>Other important SNPs:</strong></p> <p><strong><em>FCRL3</em></strong> <a href="../../snp/rs3761959/"><strong>rs3761959</strong></a><span style="font-weight: 400;">:</span></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&ldquo;T&rdquo; - correlates with Graves&rsquo; disease</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&ldquo;C&rdquo; - doesn&rsquo;t correlate with Graves&rsquo; disease</span></li> </ul> <p><strong><em>FCRL3</em></strong> <a href="../../snp/rs7522061/"><strong>rs7522061</strong></a><span style="font-weight: 400;">:</span></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&ldquo;C&rdquo; - correlates with Graves&rsquo; disease</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&ldquo;T&rdquo; - doesn&rsquo;t correlate with Graves&rsquo; disease</span></li> </ul> <h3><strong>Population Frequency&nbsp;</strong></h3> <p><span style="font-weight: 400;">As mentioned, these SNPs are almost always inherited together, so they act as a single genetic factor. Around 50% of European descendants carry one copy and 22-25% carry both copies of the alleles associated with Graves&rsquo; disease (G, T, and C, respectively).</span></p> <p><span style="font-weight: 400;">These alleles are a bit less common in East Asian populations and a bit more common in African populations, compared with Europeans.&nbsp; The &ldquo;G&rdquo; allele at rs7528684 is particularly common in African populations, where the other &ldquo;A&rdquo; allele is nearly non-existent.</span></p> <p><strong>*7267168186860269*</strong></p> <h2><strong>Recommendations to Improve Thyroid Health</strong></h2> <p><span style="font-weight: 400;">There isn't a known way to prevent Graves' disease, but your doctor can successfully treat it with medications once diagnosed. Therefore, if you're experiencing symptoms of Grave's disease &mdash; such as sudden weight loss, increased </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;">, sweating, and shaky hands &mdash; it is essential to consult with your doctor ASAP to ensure you get adequate medical care.</span></p> <p><span style="font-weight: 400;">Your doctor may suggest adding the complementary approaches mentioned below &mdash; but they should not be used to replace conventional medical treatment.</span></p> <p><span style="font-weight: 400;">In the following sections, we&rsquo;ll detail some lifestyle, diet, and supplement choices that will improve your overall health and potentially lower the impact of your FCRL3 gene on thyroid health.</span></p> <p><strong>*1713769441389416*</strong></p> <h3><strong>Lifestyle</strong></h3> <p><span style="font-weight: 400;">Extensive research has documented the adverse effects of cigarette smoking on the immune system and inflammation. It can suppress T-regs and increase NF-kB expression and thus directly worsen FCRL3-associated thyroid autoimmunity [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5868633/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361762/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/18204137"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/16387690"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Smoking has been associated with a 2x higher risk of Graves' disease and a 3-4x higher risk of Graves' ophthalmopathy (thyroid eye disease), which both correlate with FCRL3 variants [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/11331213/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/21142817/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Therefore, refrain from smoking to support your thyroid and improve overall health. And keep in mind that being around people who smoke &mdash; also known as &ldquo;second-hand&rdquo; or &ldquo;passive&rdquo; smoking &mdash; can be a significant source of exposure, too!</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Smoking suppresses T-regs, increases NF-kB, and doubles the risk of Graves' disease. Refrain from smoking and avoid passive smoke to improve your thyroid health.</span></p> <h3><strong>Supplements</strong></h3> <p><em><span style="font-weight: 400;">Keep in mind that the FDA hasn't approved the below supplements for the prevention or treatment of thyroid disorders. Always speak with your doctor before trying out any new supplements or treatment options.</span></em></p> <h4><strong>Fish Oil / Omega-3</strong></h4> <p><span style="font-weight: 400;">According to preliminary animal research, omega-3 fatty acids, abundant 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;">, can stimulate regulatory T cells. At the same time, fish oil omega-3s inhibit the inflammatory NF-kB involved in FCRL3 expression. Thanks to these effects, they may lessen the impact of your FCRL3 variants [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/24410782"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Omega-3 fatty acids from fish oil (EPA and DHA) can help with various inflammatory and autoimmune conditions. However, their effectiveness for managing autoimmune thyroid issues has not been researched in-depth [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/12480795"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">,</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/11802309"> <span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h4><strong>Probiotics</strong></h4> <p><span style="font-weight: 400;">The following probiotic strains were able to boost T-regs in mice [</span><a href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0047244"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995369/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]:</span></p> <ul> <li style="font-weight: 400;"><a href="http://selfhacked.com/blog/l-salivarius/"><span style="font-weight: 400;">L. salivarius</span></a></li> <li style="font-weight: 400;"><a href="http://selfhacked.com/blog/l-lactis/"><span style="font-weight: 400;">L. lactis</span></a></li> <li style="font-weight: 400;"><a href="https://selfhacked.com/blog/health-benefits-l-plantarum/"><span style="font-weight: 400;">L. plantarum</span></a></li> <li style="font-weight: 400;"><span style="font-weight: 400;">B. fragilis</span></li> </ul> <p><span style="font-weight: 400;">According to limited clinical evidence, microbiome disturbance plays a vital role in Graves' disease. Future research should investigate the therapeutic potential of </span><a href="https://selfhacked.com/blog/probiotics-good-bacteria/"><span style="font-weight: 400;">probiotics</span></a><span style="font-weight: 400;"> in this field [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158725/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/28689782"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><a href="https://selfhack.com/blog/treg/"><span style="font-weight: 400;">See this post for more potential ways to increase Tregs</span></a><span style="font-weight: 400;">.</span></p> <p><a href="https://selfhacked.com/blog/glucomannan-benefits/"><span style="font-weight: 400;">Glucomannan</span></a><span style="font-weight: 400;">, a prebiotic fiber, feeds the gut probiotics and relieves inflammation. It may help reduce thyroid hormones in GD patients, but the evidence is limited [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/18460488"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17027233"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/18187431-the-use-of-konjac-glucomannan-to-lower-serum-thyroid-hormones-in-hyperthyroidism/?dopt=Abstract"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p>
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91 | content_learn_more_7267168186860269_text == Some of your FCRL3 variants are slightly associated with Graves’ disease. However, keep in mind that FCRL3 is just one of many different genetic factors that can influence thyroid health. Specific dietary and lifestyle changes may counteract your FCRL3 variants and support the thyroid — read on to learn more!
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rsIDs = rs7522061,rs7528684,rs3761959
rsStatus = rs7522061,FCRL3,chr1,157698600,T,A,C,G,32,0,Normal
rsStatus = rs7528684,FCRL3,chr1,157701026,A,C,G,T,30,0,Normal
rsStatus = rs3761959,FCRL3,chr1,157699488,C,A,G,T,30,0,Normal
