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Diabetes 52:1562-1567, 2003
© 2003 by the American Diabetes Association, Inc.

Brief Genetics Reports

Polymorphisms in the Insulin-Degrading Enzyme Gene Are Associated With Type 2 Diabetes in Men From the NHLBI Framingham Heart Study

Samer Karamohamed1, Serkalem Demissie2, Jeannine Volcjak1, Chunyu Liu1, Nancy Heard-Costa1, Jun Liu1, Christina M. Shoemaker1, Carolien I. Panhuysen3, James B. Meigs4, Peter Wilson3, Larry D. Atwood1,2, L. Adrienne Cupples2, and Alan Herbert1

1 Framingham Heart Study Genetics Laboratory, Department of Neurology, Boston University School of Medicine, Boston, Massachusetts
2 Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts
3 Department of Medicine, Boston University School of Medicine, Boston, Massachusetts
4 General Internal Medicine and Clinical Epidemiology Units, General Medicine Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts

Linkage studies have mapped a susceptibility gene for type 2 diabetes to the long arm of chromosome 10, where we have previously identified a quantitative trait locus that affects fasting blood glucose within the Framingham Heart Study cohort. One candidate gene in this region is the insulin-degrading enzyme (IDE), which, in the GK rat model, has been associated with nonobese type 2 diabetes. Single nucleotide polymorphisms (SNPs) were used to map a haplotype block in the 3' end of IDE, which revealed association with HbA1c, fasting plasma glucose (FPG), and mean fasting plasma glucose (mFPG) measured over 20 years. The strongest associations were found in a sample of unrelated men. The lowest trait values were associated with a haplotype (TT, f~0.32) containing the minor allele of rs2209772 and the major allele of the rs1887922 SNP (FPG P < 0.001, mFPG P < 0.003, HbA1c P < 0.025). Another haplotype (CC, f~0.16) was associated with elevated HbA1c (P < 0.002) and type 2 diabetes (P < 0.001, odds ratio 1.96, 95% CI 1.28–3.00). The evidence presented supports the possibility that IDE is a susceptibility gene for diabetes in populations of European descent.


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