Premium
PAI‐1 Gene 4G/5G Polymorphism and Risk of Type 2 Diabetes in a Population‐based Sample
Author(s) -
Meigs James B.,
Dupuis Josée,
Liu Chunyu,
O'Donnell Christopher J.,
Fox Caroline S.,
Kathiresan Sekar,
Gabriel Stacey B.,
Larson Martin G.,
Yang Qiong,
Herbert Alan G.,
Wilson Peter W. F.,
Feng DaLi,
Tofler Geoffrey H.,
Cupples L. Adrienne
Publication year - 2006
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1038/oby.2006.85
Subject(s) - type 2 diabetes , medicine , diabetes mellitus , endocrinology , confidence interval , hazard ratio , genotype , population , plasminogen activator inhibitor 1 , body mass index , plasminogen activator , biology , genetics , gene , environmental health
Elevated plasma levels of plasminogen activator inhibitor‐1 (PAI‐1) increase risk for type 2 diabetes. The PAI‐1 4G/5G polymorphism is a major genetic determinant of plasma PAI‐1 levels, with 4G/4G homozygotes having elevated PAI‐1 levels relative to 5G allele carriers. These observations suggest the hypothesis that the PAI‐1 4G/5G polymorphism could be a genetic risk factor for diabetes. We tested this hypothesis among 2169 participants of the Framingham Offspring Study followed for seven examinations over 26 years for 216 cases of type 2 diabetes. PAI‐1 4G/4G homozygotes (genotype frequency, 27.4%) were not at significantly ( p > 0.05) increased risk of incident diabetes compared with 5G allele carriers and did not have elevated levels of diabetes‐related quantitative traits including BMI, fasting plasma glucose, or fasting insulin. In proportional hazards regression models accounting for correlation among siblings, with the 5G/5G genotype as the referent, the hazard ratio for incident diabetes for 4G/5G carriers was 0.93 (95% confidence interval, 0.68 to 1.28) and for 4G/4G carriers was 1.20 (95% confidence interval, 0.83 to 1.92). Results were not altered by further adjustment for sex or levels of BMI, triglycerides, or PAI‐1. We conclude that the PAI‐1 4G/5G polymorphism is not an important genetic risk factor for type 2 diabetes in this community‐based sample. Elevated PAI‐1 levels may be associated with an increased risk for diabetes as a marker for underlying endothelial dysfunction rather than by a direct effect of genetically mediated elevated levels.