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

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.

Pubmed ID: 20628086


  • Bailey SD
  • Xie C
  • Do R
  • Montpetit A
  • Diaz R
  • Mohan V
  • Keavney B
  • Yusuf S
  • Gerstein HC
  • Engert JC
  • Anand S
  • DREAM investigators


Diabetes care

Publication Data

October 29, 2010

Associated Grants

  • Agency: British Heart Foundation, Id: RG/08/012/25941
  • Agency: Canadian Institutes of Health Research, Id:

Mesh Terms

  • Diabetes Mellitus, Type 2
  • Edema
  • Female
  • Humans
  • Hypoglycemic Agents
  • Male
  • NFATC Transcription Factors
  • Polymorphism, Single Nucleotide
  • Ramipril
  • Thiazolidinediones