Polymorphism of the 3'-untranslated region of the leptin receptor gene, but not the adiponectin SNP45 polymorphism, predicts type 2 diabetes: a population-based study.

B ecause obesity is a powerful risk factor for the development of type 2 diabetes, genes involved in the pathogenesis of obesity might also play a role in type 2 diabetes (1). In obese subjects, heterozygous carriers of a pentanucleotide insert ion in the 3 untranslated region (UTR) of the LEPR gene had lower serum insulin concentrations than subjects homozygous for the more common deletion allele (2,3). Furthermore, in a population-based prospective study of a small number of healthy subjects, carriers of the insertion allele of the 3 -UTR LEPR polymorphism had a reduced risk of incident type 2 diabetes over 4 years compared with subjects with the deletion allele; the former also had lower fasting serum insulin levels than the latter (4). Plasma adiponectin levels are reduced in patients with obesity (5) and type 2 diabetes (6). Data from two linkage studies suggest that genetic variants of the LEPR gene are associated with insulin resistance and type 2 diabetes (7,8). Furthermore , two s ingle nucleot ide polymorphisms (SNPs) in the APM1 gene, a silent T to G substitution in exon 2 (45T/G) and a G to T substitution in intron 2 (276G/T), have been found to be associated with type 2 diabetes in Caucasian and Japanese subjects (9–11). Our aim was to evaluate the role of the I/D-LEPR polymorphism and the SNP45APM1 in the development of impaired glucose tolerance (IGT) and type 2 diabetes in the Mexico City Diabetes Study (12), a prospective population-based study with a high prevalence of type 2 diabetes.