Abstract:
:Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor-gamma (PPARG) agonists used to treat type 2 diabetes. TZDs can also be used to reduce rates of type 2 diabetes in at-risk individuals. However, a large fraction of TZD-treated patients (30-40%) do not respond to TZD treatment with an improvement in insulin sensitivity (Si). We hypothesized that variation within the gene encoding PPARG may underlie this differential response to TZD therapy. We screened approximately 40 kb of PPARG in 93 nondiabetic Hispanic women (63 responders and 30 nonresponders) with previous gestational diabetes who had participated in the Troglitazone In the Prevention Of Diabetes study. TZD nonresponse was defined as the lower tertile in change in Si after 3 months of treatment. Baseline demographic and clinical measures were not different between responders and nonresponders. We identified and genotyped 131 variants including 126 single nucleotide polymorphisms and 5 insertion-deletion polymorphisms. Linkage disequilibrium analysis identified five haplotype blocks. Eight variants were associated with TZD response (P < 0.05). Three variants were also associated with changes in Si as a continuous variable. Our results suggest that PPARG variation may underlie response to TZD therapy in women at risk for type 2 diabetes.
journal_name
Diabetesjournal_title
Diabetesauthors
Wolford JK,Yeatts KA,Dhanjal SK,Black MH,Xiang AH,Buchanan TA,Watanabe RMdoi
10.2337/diabetes.54.11.3319subject
Has Abstractpub_date
2005-11-01 00:00:00pages
3319-25issue
11eissn
0012-1797issn
1939-327Xpii
54/11/3319journal_volume
54pub_type
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