Variation in the NFATC2 (nuclear factor of activated T-cells cytoplasmic calcineurin-dependent 2) gene is associated with increased risk for rosiglitazone-associated edema, show results from a subanalysis of the DREAM trial.

The Diabetes REduction and Assessment with ramipril and rosiglitazone Medication (DREAM) trial was set up to assess whether rosiglitazone could prevent progression to Type 2 diabetes in patients with impaired fasting glucose and/or tolerance.

Consistent with previous findings, patients who were assigned to take rosiglitazone had a higher rate of congestive heart failure and peripheral edema than those who did not. Overall, 22.3% of the rosiglitazone versus 14.5% of the placebo group experienced peripheral edema.

In this study, James Engert (McGill University, Montreal, Quebec, Canada) and colleagues tested the hypothesis that the increased rate of edema with rosiglitazone could have a genetic basis. They genotyped 965 European participants in the DREAM trial for 32,088 single nucleotide polymorphisms (SNPs) with a possible association with edema.

Among the participants, 26.2% of those who received rosiglitazone and 16.1% of those who received placebo experienced edema.

One SNP, rs6123045, located in the NFATC2 gene, was significantly associated with edema in Europeans.

Among individuals treated with rosiglitazone, those with two copies of the risk allele were 2.89-fold more likely to have edema than those with two copies of the protective allele. Heterozygous individuals (one copy of each allele) had an intermediate risk. There was also an association between rs6123045 and an increased risk for edema in the participants treated with placebo, but it was nonsignificant.

The researchers tested for an interaction between the effects of rs6123045 and rosiglitazone on the risk for edema using logistic regression analysis and found that there was a significant association.

The team notes that “rs6123045 was not significantly associated with thiazolidinedione (TZD)-induced edema in Latin Americans,” but says that six other SNPs in NFATC2 did show an association with edema in both Europeans and Latin Americans.

“Identifying the specific genetic variants interacting with TZDs and resulting in edema or cardiovascular events may have important clinical consequences and enable genetic variant directed use of TZD drugs among people with dysglycemia,” suggest the authors in the journal Diabetes Care.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

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