دورية أكاديمية
Epistasis Between HLA-DRB1*16:02:01 and SLC16A11 T-C-G-T-T Reduces Odds for Type 2 Diabetes in Southwest American Indians.
| العنوان: | Epistasis Between HLA-DRB1*16:02:01 and SLC16A11 T-C-G-T-T Reduces Odds for Type 2 Diabetes in Southwest American Indians. |
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| المؤلفون: | Williams RC; Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ., Hanson RL; Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ., Peters B; La Jolla Institute for Immunology, La Jolla, CA., Kearns K; La Jolla Institute for Immunology, La Jolla, CA., Knowler WC; Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ., Bogardus C; Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ., Baier LJ; Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ. |
| المصدر: | Diabetes [Diabetes] 2024 Jun 01; Vol. 73 (6), pp. 1002-1011. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Diabetes Association Country of Publication: United States NLM ID: 0372763 Publication Model: Print Cited Medium: Internet ISSN: 1939-327X (Electronic) Linking ISSN: 00121797 NLM ISO Abbreviation: Diabetes Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Alexandria, VA : American Diabetes Association Original Publication: [New York, American Diabetes Association] |
| مواضيع طبية MeSH: | Diabetes Mellitus, Type 2*/genetics , HLA-DRB1 Chains*/genetics , Epistasis, Genetic* , Genetic Predisposition to Disease* , Monocarboxylic Acid Transporters*/genetics, Humans ; Female ; Male ; Middle Aged ; Indians, North American/genetics ; Adult ; Genotype ; Alleles ; Body Mass Index ; Haplotypes ; Polymorphism, Single Nucleotide ; Aged |
| مستخلص: | We sought to identify genetic/immunologic contributors of type 2 diabetes (T2D) in an indigenous American community by genotyping all study participants for both high-resolution HLA-DRB1 alleles and SLC16A11 to test their risk and/or protection for T2D. These genes were selected based on independent reports that HLA-DRB1*16:02:01 is protective for T2D and that SLC16A11 associates with T2D in individuals with BMI <35 kg/m2. Here, we test the interaction of the two loci with a more complete data set and perform a BMI sensitivity test. We defined the risk protection haplotype of SLC16A11, T-C-G-T-T, as allele 2 of a diallelic genetic model with three genotypes, SLC16A11*11, *12, and *22, where allele 1 is the wild type. Both earlier findings were confirmed. Together in the same logistic model with BMI ≥35 kg/m2, DRB1*16:02:01 remains protective (odds ratio [OR] 0.73), while SLC16A11 switches from risk to protection (OR 0.57 [*22] and 0.78 [*12]); an added interaction term was statistically significant (OR 0.49 [*12]). Bootstrapped (b = 10,000) statistical power of interaction, 0.4801, yielded a mean OR of 0.43. Sensitivity analysis demonstrated that the interaction is significant in the BMI range of 30-41 kg/m2. To investigate the epistasis, we used the primary function of the HLA-DRB1 molecule, peptide binding and presentation, to search the entire array of 15-mer peptides for both the wild-type and ancient human SLC16A11 molecules for a pattern of strong binding that was associated with risk and protection for T2D. Applying computer binding algorithms suggested that the core peptide at SLC16A11 D127G, FSAFASGLL, might be key for moderating risk for T2D with potential implications for type 1 diabetes. (© 2024 by the American Diabetes Association.) |
| References: | Tissue Antigens. 2009 Dec;74(6):520-33. (PMID: 19845915) Eur J Endocrinol. 2019 Feb 1;180(2):99-107. (PMID: 30475225) Nature. 2014 Jan 2;505(7481):43-9. (PMID: 24352235) Pediatr Diabetes. 2017 Dec;18(8):824-831. (PMID: 28101933) Drug Metab Pharmacokinet. 2021 Apr;37:100376. (PMID: 33561739) Cell Rep. 2019 Oct 15;29(3):781-784. (PMID: 31618644) PLoS One. 2015 May 14;10(5):e0126408. (PMID: 25973943) BMJ Open Diabetes Res Care. 2020 Jul;8(1):. (PMID: 32699108) Diabetes Metab Syndr Obes. 2019 Jun 27;12:983-989. (PMID: 31417298) Hum Immunol. 2021 Jun;82(6):385-403. (PMID: 33875299) Front Immunol. 2019 Apr 18;10:856. (PMID: 31057561) Am J Epidemiol. 1978 Dec;108(6):497-505. (PMID: 736028) Cell Rep. 2019 Jan 22;26(4):884-892.e4. (PMID: 30673611) Diabetes Metab Rev. 1990 Feb;6(1):1-27. (PMID: 2192853) Diabetologia. 2011 Jul;54(7):1684-92. (PMID: 21484216) Curr Protoc Hum Genet. 2008 Jan;Chapter 2:Unit 2.10. (PMID: 18428424) Diabetes. 2021 Apr;70(4):996-1005. (PMID: 33479058) Diabetes. 2022 Jan 21;:. (PMID: 35061024) Methods Mol Biol. 2009;578:293-306. (PMID: 19768602) Proc Natl Acad Sci U S A. 1973 Dec;70(12):3311-5. (PMID: 4519625) Annu Rev Immunol. 2016 May 20;34:335-68. (PMID: 26907215) Nucleic Acids Res. 2020 Jul 2;48(W1):W449-W454. (PMID: 32406916) Methods Mol Biol. 2011;700:77-87. (PMID: 21204028) Am J Hum Genet. 1995 Mar;56(3):799-810. (PMID: 7887436) Diabetes. 2017 Aug;66(8):2284-2295. (PMID: 28476931) Immunology. 2018 Jul;154(3):394-406. (PMID: 29315598) Nature. 2014 Feb 6;506(7486):97-101. (PMID: 24390345) Arch Endocrinol Metab. 2021 Nov 03;65(3):305-314. (PMID: 33909378) Hum Immunol. 2019 Dec;80(12):955-965. (PMID: 31706744) Immunogenetics. 2015 Nov;67(11-12):641-50. (PMID: 26416257) Sci Rep. 2019 Jan 29;9(1):843. (PMID: 30696834) Cell Rep. 2019 Oct 15;29(3):778-780. (PMID: 31618643) Gene. 2015 Jul 1;565(1):68-75. (PMID: 25839936) Cell. 2017 Jun 29;170(1):199-212.e20. (PMID: 28666119) Diabetes. 2016 Feb;65(2):510-9. (PMID: 26487785) Diabetes. 2008 Apr;57(4):1084-92. (PMID: 18252895) |
| معلومات مُعتمدة: | Intramural Research Program of the NIH, NIDDK |
| المشرفين على المادة: | 0 (SLC16A11 protein, human) |
| تواريخ الأحداث: | Date Created: 20240326 Date Completed: 20240520 Latest Revision: 20240524 |
| رمز التحديث: | 20240524 |
| مُعرف محوري في PubMed: | PMC11109785 |
| DOI: | 10.2337/db23-0925 |
| PMID: | 38530923 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1939-327X |
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| DOI: | 10.2337/db23-0925 |