{"id":6892,"date":"2025-08-16T13:00:36","date_gmt":"2025-08-16T13:00:36","guid":{"rendered":"https:\/\/autism.fratnow.com\/blog\/?p=6892"},"modified":"2025-08-21T07:12:26","modified_gmt":"2025-08-21T07:12:26","slug":"fraas-and-genetics","status":"publish","type":"post","link":"https:\/\/autism.fratnow.com\/blog\/fraas-and-genetics\/","title":{"rendered":"FRAAs and Genetics"},"content":{"rendered":"<p>[vc_row][vc_column][vc_single_image image=&#8221;6909&#8243; img_size=&#8221;full&#8221;][\/vc_column][\/vc_row][vc_row][vc_column][vc_custom_heading text=&#8221;Is There A Hidden Link Between Folate, Folate Receptor Autoantibodies, Genetics and Birth Defects?&#8221;][vc_column_text single_style=&#8221;&#8221;]For decades, doctors have recommended <strong>folic acid (FA) supplementation<\/strong> to prevent <strong><a href=\"https:\/\/autism.fratnow.com\/blog\/folate-folate-receptor-autoantibodies-neural-tube-defects\/\" target=\"_blank\" rel=\"noopener\">neural tube defects (NTDs)<\/a><\/strong> like spina bifida and anencephaly. Yet, despite widespread folate fortification programs, some women still experience NTD-affected pregnancies. Why?[\/vc_column_text][vc_column_text single_style=&#8221;&#8221;]New and ongoing research reveals a possible and surprising culprit: <a href=\"https:\/\/autism.fratnow.com\/blog\/folate-receptor-autoantibodies-in-families-with-autistic-individuals\/\" target=\"_blank\" rel=\"noopener\">folate receptor autoantibodies (FR-autoantibodies)<\/a>. These immune generated autoantibodies can <strong>block folate uptake<\/strong>, depriving a developing fetus of this crucial nutrient. Even more intriguing, <strong>genetic variations in folate metabolism<\/strong> may increase a woman\u2019s risk of producing these harmful antibodies.<br \/>\n[\/vc_column_text][vc_column_text single_style=&#8221;&#8221;]This blog breaks down a groundbreaking study that explores how genetics, <strong>folate metabolism, and autoimmunity<\/strong> intersect to potentially influence pregnancy outcomes\u2014and what it may mean for future prevention strategies.[\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column][vc_custom_heading text=&#8221;The Critical Role of Folate in Pregnancy&#8221;][vc_column_text single_style=&#8221;&#8221;]<a href=\"https:\/\/autism.fratnow.com\/blog\/importance-of-vitamin-b9-folate-for-better-brain-development-in-fetuses\/\" target=\"_blank\" rel=\"noopener\">Folate (vitamin B9)<\/a> is essential for:<br \/>\n\u2714 <strong>DNA synthesis<\/strong><br \/>\n\u2714 <strong>Cell division<\/strong><br \/>\n\u2714 <strong>Neural tube formation<\/strong> in early embryos[\/vc_column_text][vc_column_text single_style=&#8221;&#8221;]Since the body can\u2019t produce folate, we rely on:<\/p>\n<ul class=\"mr-left-ul-40\">\n<li><strong>Dietary sources<\/strong> (leafy greens, legumes, fortified grains)<\/li>\n<li><strong>Supplements<\/strong> (folic acid)<\/li>\n<\/ul>\n<p>[\/vc_column_text][vc_column_text single_style=&#8221;&#8221;]Folate is critical during pregnancy because of its involvement in all of the above. In fact, the United States\u2019 food supply is fortified with folic acid (a synthetic form of folate) in an attempt to prevent neural tube defects. Unfortunately, this action has not yet eradicated neural tube defects. There must be other underlying causes.<br \/>\n[\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column][vc_custom_heading text=&#8221;A Potential Problem? Folate Receptor Autoantibodies&#8221; use_theme_fonts=&#8221;yes&#8221;][vc_column_text single_style=&#8221;&#8221;]Normally, the <strong>folate receptor-alpha (FR-\u03b1)<\/strong> helps transport folate into cells. This is one of the main transporters of folate, which has a very high affinity for folate. But some women produce <strong>autoantibodies against this folate receptor alpha<\/strong> that:[\/vc_column_text][vc_column_text single_style=&#8221;&#8221;]\ud83d\udeab <strong>Bind to FR-\u03b1<\/strong>, blocking folate uptake (meaning folate cannot get into the cell)<br \/>\n\ud83d\udeab <strong>Increase the risk of NTDs, cleft palate, autism, and infertility<\/strong>[\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column][vc_custom_heading text=&#8221;Where Do These Autoantibodies Come From?&#8221; use_theme_fonts=&#8221;yes&#8221;][vc_column_text single_style=&#8221;&#8221;]<span style=\"font-weight: 400;\">This is a very important question, with limited research.\u00a0 But researchers believe:<\/span>[\/vc_column_text][vc_column_text single_style=&#8221;&#8221;]<\/p>\n<ol class=\"mr-left-ul-40\">\n<li><strong>High homocysteine (Hcy)<\/strong> levels (due to low folate) cause <strong>homocysteinylation<\/strong>\u2014a chemical modification of FR-\u03b1 that makes it appear &#8220;foreign&#8221; to the immune system.<\/li>\n<li>The body then <strong>attacks the modified FR-\u03b1<\/strong>, producing autoantibodies.<\/li>\n<li>These antibodies <strong>cross-react with normal FR-\u03b1<\/strong>, further disrupting folate transport.<\/li>\n<\/ol>\n<p>[\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column][vc_custom_heading text=&#8221;The Study: Genetics + Folate Receptor Autoantibodies = Higher NTD Risk?&#8221;][vc_column_text single_style=&#8221;&#8221;]A team of researchers in China and at the Baylor College of Medicine in the US investigated whether <strong>genetic variations in folate metabolism genes<\/strong> influence <strong>FR-autoantibody levels<\/strong> in pregnant women. This was a very interesting study, published in 2018 in <em>Birth Defects Research<\/em>.[\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column][vc_custom_heading text=&#8221;Who Was Studied?&#8221; font_container=&#8221;tag:h3|text_align:left&#8221; use_theme_fonts=&#8221;yes&#8221;][vc_column_text single_style=&#8221;&#8221;]<\/p>\n<ul class=\"mr-left-ul-40\">\n<li><strong>99 women<\/strong> with NTD-affected pregnancies<\/li>\n<li><strong>203 controls<\/strong> with healthy pregnancies<\/li>\n<\/ul>\n<p>[\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column][vc_custom_heading text=&#8221;Key Findings&#8221; font_container=&#8221;tag:h3|text_align:left&#8221; use_theme_fonts=&#8221;yes&#8221;][vc_column_text single_style=&#8221;&#8221;]<\/p>\n<ol class=\"mr-left-ul-40\">\n<li><strong>MTHFR rs1801133 (TT genotype)<\/strong>\n<ul class=\"mr-left-ol-40 circle-list mr-left-ul-40\">\n<li><strong>60% reduced enzyme activity<\/strong>, seemed to contribute to higher homocysteine<\/li>\n<li><strong>Strongly linked to elevated FR-autoantibodies (IgG &amp; IgM)<\/strong><\/li>\n<\/ul>\n<\/li>\n<li><strong>DNMT3A rs7560488 (TT genotype)<\/strong>\n<ul class=\"mr-left-ol-40 circle-list mr-left-ul-40\">\n<li>First study linking this variant to <strong>higher FR-autoantibody IgG<\/strong><\/li>\n<li>Previously associated with <strong>myelomeningocele (severe spina bifida)<\/strong><\/li>\n<\/ul>\n<\/li>\n<li><strong>MTHFD2 rs828903 (GG genotype)<\/strong>\n<ul class=\"mr-left-ol-40 circle-list mr-left-ul-40\">\n<li>Increased <strong>FR-autoantibody IgM<\/strong><\/li>\n<li>May disrupt mitochondrial folate metabolism<\/li>\n<\/ul>\n<\/li>\n<li><strong>No link with DHFR 19-bp deletion\/insertion<\/strong>\n<ul class=\"mr-left-ol-40 circle-list mr-left-ul-40\">\n<li>This variant didn\u2019t affect autoantibody levels<\/li>\n<\/ul>\n<\/li>\n<\/ol>\n<p>[\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column][vc_custom_heading text=&#8221;Other Observations&#8221; font_container=&#8221;tag:h3|text_align:left&#8221; use_theme_fonts=&#8221;yes&#8221;][vc_column_text single_style=&#8221;&#8221;]<\/p>\n<ul class=\"mr-left-ul-40\">\n<li><strong>Multiparous women had higher autoantibodies<\/strong> than first-time mothers.<\/li>\n<li><strong>Age, BMI, and folate supplementation<\/strong> didn\u2019t significantly affect antibody levels.<\/li>\n<\/ul>\n<p>[\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column][vc_custom_heading text=&#8221;What Does This Data Mean for Women?&#8221;][vc_column_text single_style=&#8221;&#8221;]<\/p>\n<ol class=\"mr-left-ul-40\">\n<li><strong>Not All Folate Supplements Work the Same<\/strong>\n<ul>\n<li>Women with <strong>MTHFR mutations<\/strong> may need <strong>methylfolate (5-MTHF)<\/strong> instead of folic acid. In general, it is estimated that up to <strong>30%<\/strong> of people have trouble metabolizing synthetic folic acid due to genetic variations like <strong>MTHFR mutations<\/strong>. As a result, folic acid may not be able to be properly reduced and metabolized, thereby reducing its utility. Additionally, the presence of folate receptor autoantibodies will also impede proper folate transport and function.<\/li>\n<li><strong>High-dose folate might<\/strong> overcome antibody blockage.<\/li>\n<\/ul>\n<\/li>\n<li><strong>Screening For FRAAs May Be Beneficial<\/strong>\n<ul>\n<li>Testing for <strong>FR-autoantibodies + genetic variants<\/strong> could identify high-risk women before pregnancy.<\/li>\n<li><strong>Immunomodulatory therapies<\/strong> (to reduce antibodies) may become an option. More research is required in this area.<\/li>\n<\/ul>\n<\/li>\n<li><strong>More Research Is Needed<\/strong>\n<ul>\n<li>How exactly do these genes trigger autoantibodies? This is relatively unknown, therefore additional research is necessary. Trying to unlock the mechanism behind this would be paramount!<\/li>\n<li>Will <strong>personalized folate regimens<\/strong> prevent NTDs in high-risk women? Personalized folate therapeutics may be developed if the science warrants such an endeavor!<\/li>\n<\/ul>\n<\/li>\n<\/ol>\n<p>[\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column][vc_custom_heading text=&#8221;Summary&#8221;][vc_column_text single_style=&#8221;&#8221;]This important study reveals a <strong>hidden connection between genetics, autoimmunity, and birth defects<\/strong>. While folic acid prevents many NTDs, some women remain at risk due to <strong>FR-autoantibodies driven by their DNA.<\/strong><br \/>\n[\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column][vc_custom_heading text=&#8221;Key Takeaways&#8221;][vc_column_text single_style=&#8221;&#8221;]<\/p>\n<ul>\n<li><strong>Genetic testing<\/strong> (especially MTHFR) could help tailor pregnancy care.<\/li>\n<li><strong>Future treatments<\/strong> may target autoantibodies, not just folate deficiency.<\/li>\n<li><strong>If you\u2019ve had an NTD pregnancy, ask your doctor about FR-autoantibody testing via the FRAT<sup>\u00ae<\/sup> test.<\/strong><\/li>\n<\/ul>\n<p>[\/vc_column_text][vc_column_text single_style=&#8221;&#8221;]By unraveling this complex interplay of <strong>genes, nutrition, and immunity,<\/strong> we may move closer to <strong>ending preventable birth defects<\/strong>\u2014one discovery at a time.[\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column][vc_custom_heading text=&#8221;What\u2019s Next?&#8221;][vc_column_text single_style=&#8221;&#8221;]<\/p>\n<ul class=\"mr-left-ul-40\">\n<li><strong>Should all women be screened for FR-autoantibodies with the FRAT<sup>\u00ae<\/sup> test?<\/strong>\n<ul class=\"mr-left-ol-40 circle-list mr-left-ul-40\">\n<li>This may be a good \u201c<em>Best Practices<\/em>\u201d for physicians<\/li>\n<\/ul>\n<\/li>\n<li><strong>Could this explain other pregnancy complications?<\/strong>\n<ul class=\"mr-left-ol-40 circle-list mr-left-ul-40\">\n<li>It seems quite reasonable to investigate the presence of folate receptor autoantibodies in NTDs<\/li>\n<\/ul>\n<\/li>\n<li><strong>Will CRISPR or gene therapy one day fix these mutations<\/strong>\n<ul class=\"mr-left-ol-40 circle-list mr-left-ul-40\">\n<li>To be determined! Stay tuned as science uncovers more answers!<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>[\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column][vc_column_text single_style=&#8221;&#8221;]<em><strong>Disclaimer: This blog is for informational purposes only and not medical advice. Consult a healthcare provider for personalized recommendations. The FRAT<sup>\u00ae<\/sup> test is a lab developed test performed in a CLIA certified lab. FRAT<sup>\u00ae<\/sup> is NOT approved by the FDA and requires the authorization of a physician. Please consult your medical professional for more information. <\/strong><\/em>[\/vc_column_text][\/vc_column][\/vc_row]<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Folate receptor autoantibodies, genetics &amp; folate metabolism may raise birth defect risk. Learn how testing &amp; tailored care can help prevent NTDs.<\/p>\n","protected":false},"author":1,"featured_media":6909,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[70],"tags":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v21.3 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>FRAAs and Genetics<\/title>\n<meta name=\"description\" content=\"Folate receptor autoantibodies, genetics &amp; folate metabolism may raise birth defect risk. 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