期刊
DIABETES
卷 58, 期 10, 页码 2409-2413出版社
AMER DIABETES ASSOC
DOI: 10.2337/db09-0246
关键词
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资金
- Swedish Research Council [31475113580]
- Heart and Lung Foundation
- Swedish Diabetes Research Society
- European Community [FP7/2007-2013]
- ENGAGE
- Nordic Centre of Excellence Grant in Disease Genetics
- Diabetes Programme at Lund University
- Pahlsson Foundation
- Crafoord Foundation
- Knut and Alice Wallenberg Foundation
- European Foundation for the Study of Diabetes (EFSD)
- Finnish Diabetes Research Society
- Sigrid Juselius Foundation
- Folkhalsan Research Foundation
- Signe and Ane Gyllenberg Foundation
- Swedish Cultural Foundation in Finland
- Ollqvist Foundation
- Foundation for Life and Health in Finland
- Jakobstad Hospital
- Medical Society of Finland,
- Narpes Research Foundation
- Vasa and Narpes Health Centers
- [HEALTH-F4-2007-201413]
OBJECTIVE-Two independent genome-wide association studies for type 2 diabetes in Japanese subjects have recently identified common variants in the KCNQ1 gene that are strongly associated with type 2 diabetes. Here we studied whether a common variant in KCNQ1 would influence BMI as well as insulin secretion and action and predict future type 2 diabetes in subjects from Sweden and Finland. RESEARCH DESIGN AND METHODS-Risk of type 2 diabetes conferred by KCNQ1 rs2237895 was studied in 2,830 type 2 diabetic case subjects and 3,550 control subjects from Sweden (Malmo Case-Control) and prospectively in 16,061 individuals from the Malmo Preventive Project (MPP). Association between genotype and insulin secretion/action was assessed cross-sectionally in 3,298 nondiabetic subjects from the Prevalence, Prediction and Prevention of Diabetes (PPP)-Botnia Study and longitudinally in 2,328 nondiabetic subjects from the Botnia Prospective Study (BPS). KCNQ1 expression (n = 18) and glucose-stimulated insulin secretion (n = 19) were measured in human islets from nondiabetic cadaver donors. RESULTS-The C-allele of KCNQ1 rs2237895 was associated with increased risk of type 2 diabetes in both the Malmo Case-Control (odds ratio 1.23 [95% CI 1.12-1.34]; P = 5.6 X 10(-6)) and the prospective (1.14 [1.06-1.22]; P = 4.8 X 10(-4)) studies. Furthermore, the C-allele was associated with decreased insulin secretion (corrected insulin response [CIR] P = 0.013; disposition index [DI] P = 0.013) in the PPP-Botnia Study and in the BPS at baseline (CIR P = 3.6 X 10(-4); DI P = 0.0058) and after follow-up (CIR P = 0.0018; DI P = 0.0030). C-allele carriers showed reduced glucose-stimulated insulin secretion in human islets (P = 2.5 X 10(-6)). CONCLUSIONS-A common variant in the KCNQ1 gene is associated with increased risk of future type 2 diabetes in Scandinavians, which partially can be explained by an effect on insulin secretion. Diabetes 58:2409-2413, 2009
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