Combination of polypmorphisms in OB-R and the OB gene associated with insulin resistance in Nauruan males

OBJECTIVE: To investigate the relationship between polymorphisms in the OB- R and OB genes and metabolic markers for obesity and glucose intolerance in a population of Nauruan men. In addition, we examined the effect of the si multaneous presence of the three polymorphisms on the phenotype of individu als in this population. DESIGN AND SUBJECTS: This study was conducted in a population from the Paci fic Island of Nauru, Populations in this region have some of the highest re corded rates of obesity and type 2 diabetes and are therefore of great inte rest in the genetic analysis of these diseases. Two hundred and thirty-two male subjects were examined in this cross-sectional study, All subjects wer e non-diabetic and the group had a mean age of 31 y and a mean body weight of 104 kg, MEASUREMENTS: Several phenotypic measures of body fatness and fat distribut ion (anthropometry), fasting plasma insulin, glucose and leptin concentrati ons, blood pressure and 2 h plasma glucose concentration, genotypes of subj ects for the Gln223Arg, PRO1019pro (OB-R gene) and OB gene polymorphisms. RESULTS: Individually, the OB gene and Gln223Arg OB-R polymorphisms were no t associated with the obese or glucose-intolerant phenotype in this populat ion. Individuals with the PRO1019pro polymorphism were found to have elevat ed insulin concentrations and diastolic blood pressure (P-c = 0.04), In add ition, individuals found to simultaneously exhibit homozygosity of the comm on allele of all three polymorphisms (genotypes: Arg/Arg, pro/pro and II/II ) exhibited significantly elevated fasting insulin levels (P-c = 0.03), CONCLUSIONS: Pacific Island populations exhibit a remarkably high prevalenc e rate of obesity and type 2 diabetes and represent a unique population for genetic studies of obesity. In the present study we have revealed that a s pecific combination of alleles in OB and OB-R, two candidate genes for obes ity, may confer an increased risk for the development of insulin resistance in Nauruan males.