Genetics of the APM1 locus and its contribution to type 2 diabetes susceptibility in French Caucasians.

Abstract

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.

• Authors: Fernando Gibson, Philippe Froguel
• Journal: Diabetes (Diabetes) Vol. 53 Issue 11 Pg. 2977-83 (Nov 2004) ISSN: 0012-1797 [Print] United States
• PMID: 15504979 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adiponectin
• Intercellular Signaling Peptides and Proteins

Topics

• Adiponectin
• Chromosome Mapping
• Diabetes Mellitus, Type 2 (epidemiology, genetics)
• France
• Genetic Predisposition to Disease
• Humans
• Intercellular Signaling Peptides and Proteins (genetics)
• Polymorphism, Single Nucleotide (genetics)
• Promoter Regions, Genetic (genetics)
• Risk Factors
• White People