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
- Monica Nannipieri, MD1,
- Rosalinda Posadas, PHD1,
- Alessandra Bonotti, BM1,
- Ken Williams2,
- Clicerio Gonzalez-Villalpando, MD3,
- Michael P. Stern, MD2 and
- Ele Ferrannini, MD1
- 1Internal Medicine and Metabolism Institute of Clinical Physiology, University of Pisa, Pisa, Italy
- 2Division of Clinical Epidemiology, University of Texas Health Science Center, San Antonio, Texas
- 3Centro de Estudios en Diabetes, American British Cowdray Hospital, Mexico City, Mexico
- Address correspondence and reprint requests to Dr. Monica Nannipieri, Internal Medicine, Institute of Clinical Psychology, University of Pisa, Via Roma, 67, 56100 Pisa, Italy. E-mail: nannipi{at}ifc.cnr.it
- IGT, impaired glucose tolerance
- NGT, normal glucose tolerance
- SNP, single nucleotide polymorphism
- UTR, untranslated region
Because 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 insertion 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 single nucleotide 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 SNP45-APM1 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.
RESEARCH DESIGN AND METHODS—
Anthropometric and clinical parameters were measured as described elsewhere …
