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Diabetes 53:2977-2983, 2004
© 2004 by the American Diabetes Association, Inc.

Genetics of the APM1 Locus and Its Contribution to Type 2 Diabetes Susceptibility in French Caucasians

Fernando Gibson1, and Philippe Froguel1,2

1 Genomic Medicine, Imperial College, London, U.K
2 CNRS 8090, Institut de Biologie de Lille, Institut Pasteur, Lille, France

We have carried out a detailed reexamination of the genetics of the APM1 locus and its contribution to the genetic basis of type 2 diabetes susceptibility in the French Caucasian population. The G allele of single nucleotide polymorphism –11426 in the APM1 promoter showed modest association with type 2 diabetes (odds ratio 1.44 [95% CI 1.04–1.98]; P = 0.03), providing corroborative evidence that single nucleotide polymorphisms in the APM1 promoter region contribute to the genetic risk of type 2 diabetes. A "sliding window" analysis identified haplotypes 1-1-1, 1-1-1-1, and 1-1-1-1-1 as being strongly protective against type 2 diabetes (P ≤ 0.0001). Evidence is presented that the APM1 gene is a locus of low linkage disequilibrium, high haplotype diversity, and high recombination. We were unable to obtain data to support the hypothesis that genetic variation in the APM1 gene is a major contributor to the type 2 diabetes linkage result at chromosome 3q27. Finally, in families with early-onset type 2 diabetes, we obtained suggestive evidence of a linkage peak for serum adiponectin levels (logarithm of odds = 2.1) that closely matched the position of the type 2 diabetes linkage peak. This result indicated that the type 2 diabetes susceptibility locus at 3q27 influences both genetic predisposition to type 2 diabetes and serum adiponectin levels in patients with type 2 diabetes.

Address correspondence and reprint requests to Fernando Gibson, Genomic Medicine, Imperial College, Hammersmith Campus, Du Cane Road, London W12 0NN, U.K. E-mail: fernando.gibson{at}imperial.ac.uk


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Copyright © 2004 by the American Diabetes Association.