The Influence of Rare Genetic Variation in SLC30A8 on Diabetes Incidence and β-Cell Function
| العنوان: | The Influence of Rare Genetic Variation in SLC30A8 on Diabetes Incidence and β-Cell Function |
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| المؤلفون: | Nisa M. Maruthur, Dana Dabelea, Jarred B. McAteer, Rebecca R. Fanelli, Steven E. Kahn, Elizabeth J. Mayer-Davis, Kathleen A. Jablonski, William C. Knowler, Robert L. Hanson, Jose C. Florez, Candace Guiducci, Alan R. Shuldiner, Paul W. Franks, Rachel J. Ackerman, Liana K. Billings, Andrew W. Taylor, Linda M. Delahanty |
| المصدر: | The Journal of Clinical Endocrinology & Metabolism. 99:E926-E930 |
| بيانات النشر: | The Endocrine Society, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Adult, Male, medicine.medical_specialty, Diabetes risk, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Context (language use), Zinc Transporter 8, Type 2 diabetes, Biology, Polymorphism, Single Nucleotide, Biochemistry, Endocrinology, Gene Frequency, Insulin-Secreting Cells, Internal medicine, Diabetes mellitus, Insulin Secretion, medicine, Humans, Insulin, Genetic Predisposition to Disease, Cation Transport Proteins, Allele frequency, Alleles, Genetic Association Studies, Framingham Risk Score, JCEM Online: Advances in Genetics, SLC30A8, Incidence, Biochemistry (medical), Middle Aged, medicine.disease, Diabetes Mellitus, Type 2, biology.protein, Female |
| الوصف: | The variant rs13266634 in SLC30A8, encoding a β-cell-specific zinc transporter, is associated with type 2 diabetes. We aimed to identify other variants in SLC30A8 that increase diabetes risk and impair β-cell function, and test whether zinc intake modifies this risk. DESIGN/OUTCOME: We sequenced exons in SLC30A8 in 380 Diabetes Prevention Program (DPP) participants and identified 44 novel variants, which were genotyped in 3445 DPP participants and tested for association with diabetes incidence and measures of insulin secretion and processing. We examined individual common variants and used gene burden tests to test 39 rare variants in aggregate.We detected a near-nominal association between a rare-variant genotype risk score and diabetes risk. Five common variants were associated with the oral disposition index. Various methods aggregating rare variants demonstrated associations with changes in oral disposition index and insulinogenic index during year 1 of follow-up. We did not find a clear interaction of zinc intake with genotype on diabetes incidence.Individual common and an aggregate of rare genetic variation in SLC30A8 are associated with measures of β-cell function in the DPP. Exploring rare variation may complement ongoing efforts to uncover the genetic influences that underlie complex diseases. |
| تدمد: | 1945-7197 0021-972X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::44530bc0731fd66a2956e4938dab1a5b https://doi.org/10.1210/jc.2013-2378 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....44530bc0731fd66a2956e4938dab1a5b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19457197 0021972X |
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