Systematic evaluation of validated type 2 diabetes and glycaemic trait loci for association with insulin clearance
| العنوان: | Systematic evaluation of validated type 2 diabetes and glycaemic trait loci for association with insulin clearance |
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| المؤلفون: | Thomas A. Buchanan, Talin Haritunians, Matthew Jones, Jerome I. Rotter, Kent D. Taylor, Jinrui Cui, Anny H. Xiang, Mark O. Goodarzi, Y. D.I. Chen, Xiuqing Guo, Leslie J. Raffel, Willa A. Hsueh |
| المصدر: | Diabetologia. 56:1282-1290 |
| بيانات النشر: | Springer Science and Business Media LLC, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Adult, Blood Glucose, Male, Linkage disequilibrium, medicine.medical_specialty, Time Factors, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Type 2 diabetes, Biology, Quantitative trait locus, Polymorphism, Single Nucleotide, Linkage Disequilibrium, Article, Cohort Studies, Delta-5 Fatty Acid Desaturase, Insulin resistance, Internal medicine, Internal Medicine, medicine, Humans, Insulin, Glycated Hemoglobin, Genetic Variation, Type 2 Diabetes Mellitus, Hispanic or Latino, Middle Aged, Glucose clamp technique, medicine.disease, Phenotype, Endocrinology, Diabetes Mellitus, Type 2, Hyperglycemia, Glucose Clamp Technique, Trait, Female, Insulin Resistance |
| الوصف: | Insulin clearance is a highly heritable trait, for which few quantitative trait loci have been discovered. We sought to determine whether validated type 2 diabetes and/or glycaemic trait loci are associated with insulin clearance.Hyperinsulinaemic-euglycaemic clamps were performed in two Hispanic-American family cohorts totalling 1329 participants in 329 families. The Metabochip was used to fine-map about 50 previously identified loci for type 2 diabetes, fasting glucose, fasting insulin, 2 h glucose or HbA1c. This resulted in 17,930 variants, which were tested for association with clamp-derived insulin clearance via meta-analysis of the two cohorts.In the meta-analysis, 38 variants located within seven loci demonstrated association with insulin clearance (p0.001). The top signals for each locus were rs10241087 (DGKB/TMEM195 [TMEM195 also known as AGMO]) (p = 4.4 × 10(-5)); chr1:217605433 (LYPLAL1) (p = 3.25 × 10(-4)); rs2380949 (GLIS3) (p = 3.4 × 10(-4)); rs55903902 (FADS1) (p = 5.6 × 10(-4)); rs849334 (JAZF1) (p = 6.4 × 10(-4)); rs35749 (IGF1) (p = 6.7 × 10(-4)); and rs9460557 (CDKAL1) (p = 6.8 × 10(-4)).While the majority of validated loci for type 2 diabetes and related traits do not appear to influence insulin clearance in Hispanics, several of these loci do show evidence of association with this trait. It is therefore possible that these loci could have pleiotropic effects on insulin secretion, insulin sensitivity and insulin clearance. |
| تدمد: | 1432-0428 0012-186X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c8ad766dfad3daf97e6cb7f19da66c3dTest https://doi.org/10.1007/s00125-013-2880-6Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c8ad766dfad3daf97e6cb7f19da66c3d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14320428 0012186X |
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