{"id":38817,"date":"2023-03-10T06:10:25","date_gmt":"2023-03-10T11:10:25","guid":{"rendered":"https:\/\/nebula.org\/blog\/?p=38817"},"modified":"2023-05-12T08:31:39","modified_gmt":"2023-05-12T12:31:39","slug":"slc30a8-mutations-protect-in-type-2-diabetes","status":"publish","type":"post","link":"https:\/\/nebula.org\/blog\/slc30a8-mutations-protect-in-type-2-diabetes\/","title":{"rendered":"Several SLC30A8 mutations may protect in type 2 diabetes"},"content":{"rendered":"\n<p><a href=\"https:\/\/nebula.org\/blog\/is-diabetes-genetic\/\">Type 2 diabetes<\/a> (T2D) is a chronic condition in which the body does not produce or respond correctly to insulin, resulting in elevated blood glucose levels. Although diabetes is diagnosed primarily in adults, its onset can start as early as childhood. Did you know that certain mutations in the SLC30A8 gene may offer some protection against it?<\/p>\n\n\n\n<p>There is no cure. However, diet and exercise can help patients manage the condition. Sometimes, insulin therapy is also needed.&nbsp;<\/p>\n\n\n\n<p>The exact cause of the disease is unknown. However, experts agree that being overweight and inactivity are risk factors. Having a family history also increases T2D risk.<\/p>\n\n\n\n<figure class=\"wp-block-image aligncenter size-large is-resized\"><img decoding=\"async\" src=\"https:\/\/nebula.org\/blog\/wp-content\/uploads\/2023\/03\/running-1024x682.jpg\" alt=\"Person running\" class=\"wp-image-38826\" width=\"768\" height=\"512\" srcset=\"https:\/\/nebula.org\/blog\/wp-content\/uploads\/2023\/03\/running.jpg 924w, https:\/\/nebula.org\/blog\/wp-content\/uploads\/2023\/03\/running-300x200.jpg 300w, https:\/\/nebula.org\/blog\/wp-content\/uploads\/2023\/03\/running-768x511.jpg 768w\" sizes=\"(max-width: 768px) 100vw, 768px\" \/><figcaption class=\"wp-element-caption\">Exercise can lower diabetes risk. Photo by<a href=\"https:\/\/unsplash.com\/@jennyhill?utm_source=unsplash&amp;utm_medium=referral&amp;utm_content=creditCopyText\" target=\"_blank\" rel=\"noreferrer noopener\"> Jenny Hill<\/a> on<a href=\"https:\/\/unsplash.com\/photos\/mQVWb7kUoOE?utm_source=unsplash&amp;utm_medium=referral&amp;utm_content=creditCopyText\" target=\"_blank\" rel=\"noreferrer noopener\"> Unsplash<\/a><\/figcaption><\/figure>\n\n\n\n<p>Chronically high insulin levels in the bloodstream, as occurs in type 2 diabetes, can create serious complications. Specifically, it increases the risk of conditions such as <a href=\"https:\/\/nebula.org\/blog\/is-heart-disease-genetic\/\">heart disease<\/a>, nerve damage, <a href=\"https:\/\/nebula.org\/blog\/is-kidney-disease-genetic\/\">kidney disease<\/a>, eye damage, slow healing, sleep apnea, and <a href=\"https:\/\/nebula.org\/blog\/is-dementia-genetic\/\">dementia<\/a>.<\/p>\n\n\n\n<p>The most effective way to prevent or manage type 2 diabetes is a healthy lifestyle. These recommendations include eating foods low in fat and high in fiber, avoiding inactivity for long periods, and losing weight.<\/p>\n\n\n\n<p>While good eating and exercise habits will always have an impact, human genetics plays a role too. A study published in <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4051628\/\" target=\"_blank\" rel=\"noreferrer noopener\"><em>Nature Genetics<\/em><\/a> found 12 genetic mutations that protect against type 2 diabetes. These variants are rare (&lt;0.1% frequency) in the general population.<\/p>\n\n\n\n<p>Did you know that some rare variants can offer protection from type 2 diabetes? The majority of the population does not have them, which is normal. However, the folks that do get some extra protection.&nbsp;<\/p>\n\n\n\n<figure class=\"wp-block-table\"><table class=\"has-background\" style=\"background-color:#fcf0ef\"><tbody><tr><td class=\"has-text-align-center\" data-align=\"center\"><strong>You can use the Nebula Gene Analysis Tool to find this gene and see if you have these functional variants. Keep reading to learn what these mutations are and how you can check your status.<\/strong><\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"h-the-study\">The Study<\/h2>\n\n\n\n<p>Overall, the authors of this study sequenced ~150,000 individuals across five ethnicities.<\/p>\n\n\n\n<p>The gene <em>SLC30A8<\/em> encodes a certain kind of protein known as a zinc transporter. This protein is involved with insulin crystallization. Furthermore, <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3442244\/\" target=\"_blank\" rel=\"noreferrer noopener\">previous studies<\/a> have identified a common variant in this gene related to type 2 diabetes risk. This background suggests that there may be other variants on this gene and around the SNP related to type 2 diabetes. <\/p>\n\n\n\n<p>Specifically, the authors of the <em>Nature Genetics<\/em> paper were looking for protective variants that may also be therapeutic targets.&nbsp;&nbsp;<\/p>\n\n\n\n<p>Initial sequencing in 758 individuals from Finland or Sweden, followed by another analysis on 21,000 individuals, found two potentially relevant variants on the <em>SLC30A8<\/em> gene. The one found in the second analysis was confirmed by a larger European dataset.<\/p>\n\n\n\n<p>Beyond these initial results, the group sought to identify additional mutations that may represent more diverse populations.&nbsp;<\/p>\n\n\n\n<p>Using a curated dataset of 35 million variants, they found another protein-truncating variant in <em>SLC30A8 <\/em>also associated with a significant reduction in type 2 diabetes risk (they observed the mutation in 0.03% of type 2 diabetes cases versus 0.18% in non-diabetic controls).&nbsp;<\/p>\n\n\n\n<figure class=\"wp-block-image aligncenter size-large is-resized\"><img decoding=\"async\" src=\"https:\/\/nebula.org\/blog\/wp-content\/uploads\/2023\/03\/diabetes-testing-1024x683.jpg\" alt=\"Diabetes management tools\" class=\"wp-image-38818\" width=\"768\" height=\"512\" srcset=\"https:\/\/nebula.org\/blog\/wp-content\/uploads\/2023\/03\/diabetes-testing.jpg 924w, https:\/\/nebula.org\/blog\/wp-content\/uploads\/2023\/03\/diabetes-testing-300x200.jpg 300w, https:\/\/nebula.org\/blog\/wp-content\/uploads\/2023\/03\/diabetes-testing-768x512.jpg 768w\" sizes=\"(max-width: 768px) 100vw, 768px\" \/><figcaption class=\"wp-element-caption\">Diabetes testing and management. Photo by<a href=\"https:\/\/unsplash.com\/@towfiqu999999?utm_source=unsplash&amp;utm_medium=referral&amp;utm_content=creditCopyText\" target=\"_blank\" rel=\"noreferrer noopener\"> Towfiqu barbhuiya<\/a> on<a href=\"https:\/\/unsplash.com\/photos\/ZJaK9jQXeDA?utm_source=unsplash&amp;utm_medium=referral&amp;utm_content=creditCopyText\" target=\"_blank\" rel=\"noreferrer noopener\"> Unsplash<\/a><\/figcaption><\/figure>\n\n\n\n<p>Finally, they performed exome sequencing on about 12,000 individuals including African American, East Asian, European, Hispanic, and South Asian subjects, which revealed nine additional protein-truncating proteins.<\/p>\n\n\n\n<p>When they combined all sequencing data, the authors found that heterozygosity for any of the 12 protein-truncating variants was associated with 65% reduced type 2 diabetes risk. The chances of having one of these mutations in the general population are less than 1%.&nbsp;<br>Because these mutations are loss-of-function variants (they inactivate one copy of <em>SLC30A8<\/em>) that protect against disease, they could be effective targets for future drugs designed to prevent disease.&nbsp;<\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"h-explore-your-genome\">Explore your Genome!<\/h2>\n\n\n\n<figure class=\"wp-block-table\"><table class=\"has-background\" style=\"background-color:#fcf0ef\"><tbody><tr><td class=\"has-text-align-center\" data-align=\"center\"><strong>Did you know you can use the Nebula Gene Analysis Tool (available with Deep and Ultra Deep WGS) to check whether you have these protective variants?<\/strong><\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<p>This tool empowers you to examine any gene in your genome and identify important genetic variants and mutations.&nbsp;<\/p>\n\n\n\n<ol class=\"wp-block-list\">\n<li>When you click on the \u201cGet Started\u201d button your VCF file will be loaded into the Gene Analysis tool in a new tab.<\/li>\n\n\n\n<li>Type \u201cSLC30A8\u201d into the search bar at the top.&nbsp;<\/li>\n\n\n\n<li>The Gene Analysis tool will extract genetic variants in the <em>SLC30A8<\/em> gene from your VCF file and display them to you using symbols that have different colors. The colors denote the potential importance of variants. The Gene Analysis tool determines this by referencing the ClinVar database and other resources.<\/li>\n\n\n\n<li><strong>Any<\/strong> red and orange variants could potentially be important. Click on them to check if any of them are truncating variants like the ones described in the study described above.<\/li>\n<\/ol>\n\n\n\n<p>12 variants discovered to truncate SLC30A8<\/p>\n\n\n\n<ol class=\"wp-block-list\">\n<li>p.Arg138X<\/li>\n\n\n\n<li>p.Lys34SerfsX50<\/li>\n\n\n\n<li>c.71+2T&gt;A<\/li>\n\n\n\n<li>p.Met50Ile<\/li>\n\n\n\n<li>c.271+G&gt;A<\/li>\n\n\n\n<li>c.419-1G&gt;C<\/li>\n\n\n\n<li>p.Trp152X<\/li>\n\n\n\n<li>p.Gln174X<\/li>\n\n\n\n<li>c.572+1G&gt;A<\/li>\n\n\n\n<li>p.Tyr284X<\/li>\n\n\n\n<li>p.Ile291PhefsX2<\/li>\n\n\n\n<li>p.Ser327ThrafsX5<\/li>\n<\/ol>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"h-citation\">Citation<\/h2>\n\n\n\n<p><em>Flannick J, Thorleifsson G, Beer NL, Jacobs SB, Grarup N, Burtt NP, Mahajan A, Fuchsberger C, Atzmon G, Benediktsson R, Blangero J, Bowden DW, Brandslund I, Brosnan J, Burslem F, Chambers J, Cho YS, Christensen C, Douglas DA, Duggirala R, Dymek Z, Farjoun Y, Fennell T, Fontanillas P, Fors\u00e9n T, Gabriel S, Glaser B, Gudbjartsson DF, Hanis C, Hansen T, Hreidarsson AB, Hveem K, Ingelsson E, Isomaa B, Johansson S, J\u00f8rgensen T, J\u00f8rgensen ME, Kathiresan S, Kong A, Kooner J, Kravic J, Laakso M, Lee JY, Lind L, Lindgren CM, Linneberg A, Masson G, Meitinger T, Mohlke KL, <\/em><\/p>\n\n\n\n<p><em>Molven A, Morris AP, Potluri S, Rauramaa R, Ribel-Madsen R, Richard AM, Rolph T, Salomaa V, Segr\u00e8 AV, Sk\u00e4rstrand H, Steinthorsdottir V, Stringham HM, Sulem P, Tai ES, Teo YY, Teslovich T, Thorsteinsdottir U, Trimmer JK, Tuomi T, Tuomilehto J, Vaziri-Sani F, Voight BF, Wilson JG, Boehnke M, McCarthy MI, Nj\u00f8lstad PR, Pedersen O; Go-T2D Consortium; T2D-GENES Consortium; Groop L, Cox DR, Stefansson K, Altshuler D. Loss-of-function mutations in SLC30A8 protect against type 2 diabetes. Nat Genet. 2014 Apr;46(4):357-63. doi: 10.1038\/ng.2915. Epub 2014 Mar 2. PMID: 24584071; PMCID: PMC4051628.<\/em><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Type 2 diabetes (T2D) is a chronic condition in which the body does not produce or respond correctly to insulin, resulting in elevated blood glucose levels. Although diabetes is diagnosed primarily in adults, its onset can start as early as &hellip;<\/p>\n<p class=\"read-more\"> <a class=\"ast-button\" href=\"https:\/\/nebula.org\/blog\/slc30a8-mutations-protect-in-type-2-diabetes\/\"> <span class=\"screen-reader-text\">Several SLC30A8 mutations may protect in type 2 diabetes<\/span> Read More \u00bb<\/a><\/p>\n","protected":false},"author":18,"featured_media":38834,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"om_disable_all_campaigns":false,"site-sidebar-layout":"default","site-content-layout":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","_FSMCFIC_featured_image_caption":"Blood sugar check. Shutterstock.","_FSMCFIC_featured_image_nocaption":"","_FSMCFIC_featured_image_hide":"","footnotes":""},"categories":[2350],"tags":[],"class_list":["post-38817","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v20.13 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Several SLC30A8 mutations may protect in type 2 diabetes<\/title>\n<meta name=\"description\" content=\"Genetic mutations in the SLC30A8 gene may protect against type 2 diabetes. Learn whether you have these protective variants here!\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/nebula.org\/blog\/slc30a8-mutations-protect-in-type-2-diabetes\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Several SLC30A8 mutations may protect in type 2 diabetes\" \/>\n<meta property=\"og:description\" content=\"Genetic mutations in the SLC30A8 gene may protect against type 2 diabetes. Learn whether you have these protective variants here!\" \/>\n<meta property=\"og:url\" content=\"https:\/\/nebula.org\/blog\/slc30a8-mutations-protect-in-type-2-diabetes\/\" \/>\n<meta property=\"og:site_name\" content=\"Nebula Genomics Blog\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/facebook.com\/nebulagenomics\" \/>\n<meta property=\"article:published_time\" content=\"2023-03-10T11:10:25+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2023-05-12T12:31:39+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/nebula.org\/blog\/wp-content\/uploads\/2023\/03\/diabetes.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"924\" \/>\n\t<meta property=\"og:image:height\" content=\"617\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"Christina Swords, Ph.D.\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:creator\" content=\"@nebulagenomics\" \/>\n<meta name=\"twitter:site\" content=\"@nebulagenomics\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Christina Swords, Ph.D.\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"5 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\/\/nebula.org\/blog\/slc30a8-mutations-protect-in-type-2-diabetes\/#article\",\"isPartOf\":{\"@id\":\"https:\/\/nebula.org\/blog\/slc30a8-mutations-protect-in-type-2-diabetes\/\"},\"author\":{\"name\":\"Christina Swords, Ph.D.\",\"@id\":\"https:\/\/nebula.org\/blog\/#\/schema\/person\/97db973a52b62c2cb68bcf104374a772\"},\"headline\":\"Several SLC30A8 mutations may protect in type 2 diabetes\",\"datePublished\":\"2023-03-10T11:10:25+00:00\",\"dateModified\":\"2023-05-12T12:31:39+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\/\/nebula.org\/blog\/slc30a8-mutations-protect-in-type-2-diabetes\/\"},\"wordCount\":1004,\"publisher\":{\"@id\":\"https:\/\/nebula.org\/blog\/#organization\"},\"articleSection\":[\"Science\"],\"inLanguage\":\"en-US\"},{\"@type\":\"WebPage\",\"@id\":\"https:\/\/nebula.org\/blog\/slc30a8-mutations-protect-in-type-2-diabetes\/\",\"url\":\"https:\/\/nebula.org\/blog\/slc30a8-mutations-protect-in-type-2-diabetes\/\",\"name\":\"Several SLC30A8 mutations may protect in type 2 diabetes\",\"isPartOf\":{\"@id\":\"https:\/\/nebula.org\/blog\/#website\"},\"datePublished\":\"2023-03-10T11:10:25+00:00\",\"dateModified\":\"2023-05-12T12:31:39+00:00\",\"description\":\"Genetic mutations in the SLC30A8 gene may protect against type 2 diabetes. 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