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Diabetes Care. 2010 Oct;33(10):2250-3. doi: 10.2337/dc10-0452. Epub 2010 Jul 13.

Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.

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  • 1Department of Human Genetics, McGill University, Montreal, Quebec, Canada.

Abstract

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 × 10(-7), corrected P = 0.017). Homozygous individuals had the highest edema rate (hazard ratio 2.89, P = 4.22 × 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 × 10(-3)). Six SNPs in NFATC2 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.

PMID:
20628086
[PubMed - indexed for MEDLINE]
PMCID:
PMC2945168
Free PMC Article

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