Genetics of the APM1 locus and its contribution to type 2 diabetes susceptibility in French Caucasians.
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.
Gibson
Fernando
F
Genomic Medicine, Imperial College, Hammersmith Campus, Du Cane Road, London W12 0NN, UK. fernando.gibson@imperial.ac.uk.
Froguel
Philippe
P
D052242:Adiponectin; D002874:Chromosome Mapping; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics*; D005602:France; D020022:Genetic Predisposition to Disease; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors; D044465:White People
D052242:Adiponectin; D036341:Intercellular Signaling Peptides and Proteins