期刊
DIABETES CARE
卷 33, 期 10, 页码 2250-2253出版社
AMER DIABETES ASSOC
DOI: 10.2337/dc10-0452
关键词
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资金
- Heart and Stroke Foundation of Ontario [NA 5754]
- Canadian Institutes of Health Research (CIHR) [1508000]
- GSK
- Sanofi-aventis
- King Pharma
- British Heart Foundation [RG/08/012/25941] Funding Source: researchfish
OBJECTIVE - Thiazolidinediones are used to treat type 2 diabetes. Their use has been associated with peripheral edema and congestive heart failure outcomes that may have a genetic etiology. RESEARCH DESIGN AND METHODS - We genotyped 4,197 participants of the multiethnic DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) trial with a 50k single nucleotide polymorphisms (SNP) array, which captures 2000 cardiovascular, inflammatory, and metabolic genes. We tested 32,088 SNPs for an association with edema among Europeans who received rosiglitazone (n = 965). RESULTS - One SNP, rs6123045, in NFATC2 was significantly associated with edema (odds ratio 1.89 [95% CI 1.47-2.42]; P = 5.32 x 10(-7), corrected P = 0.01.7). Homozygous individuals had the highest edema rate (hazard ratio 2.89, P = 4.22 x 10(-4)) when compared with individuals homozygous for the protective allele, with heterozygous individuals having an intermediate risk. The interaction between the SNP and rosiglitazone for edema was significant (P = 7.68 x 10(-3)). Six SNPs in NEATC2 were significant in both Europeans and Latin Americans (P < 0.05). CONCLUSIONS - Genetic variation at the NFATC2 locus contributes to edema among individuals who receive rosiglitazone.
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