Combination of polymorphisms 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 simultaneous presence of the three polymorphisms on the phenotype of individuals in this population.


METHODS
This study was conducted in a population from the Pacific Island of Nauru. Populations in this region have some of the highest recorded rates of obesity and type 2 diabetes and are therefore of great interest in the genetic analysis of these diseases. Two hundred and thirty-two male subjects were examined in this cross-sectional study. All subjects were non-diabetic and the group had a mean age of 31 y and a mean body weight of 104 kg.


METHODS
Several phenotypic measures of body fatness and fat distribution (anthropometry), fasting plasma insulin, glucose and leptin concentrations, blood pressure and 2 h plasma glucose concentration, genotypes of subjects for the Gln223Arg, PRO1019pro (OB-R gene) and OB gene polymorphisms.


RESULTS
Individually, the OB gene and Gln223Arg OB-R polymorphisms were not associated with the obese or glucose-intolerant phenotype in this population. Individuals with the PRO1019pro polymorphism were found to have elevated insulin concentrations and diastolic blood pressure (Pc = 0.04). In addition, individuals found to simultaneously exhibit homozygosity of the common allele of all three polymorphisms (genotypes: Arg/Arg, pro/pro and II/II) exhibited significantly elevated fasting insulin levels (Pc = 0.03).


CONCLUSIONS
Pacific Island populations exhibit a remarkably high prevalence 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 specific combination of alleles in OB and OB-R, two candidate genes for obesity, may confer an increased risk for the development of insulin resistance in Nauruan males.
de Silva
A M
AM
Metabolic Research Unit, School of Nutrition and Public Health, Deakin University, Geelong, Australia.
Walder
K R
KR
Aitman
T J
TJ
Gotoda
T
T
Goldstone
A P
AP
Hodge
A M
AM
de Courten
M P
MP
Zimmet
P Z
PZ
Collier
G R
GR
D000328:Adult; D000368:Aged; D000886:Anthropometry; D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008849:Micronesia; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D044465:White People / Q000235:genetics
D002352:Carrier Proteins; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin