The G1057D polymorphism of IRS-2 gene and its relationship with obesity in conferring susceptibility to type 2 diabetes in Asian Indians.
OBJECTIVE
To investigate the association of insulin receptor substrate-2 (IRS-2) G1057D polymorphism with type 2 diabetes and obesity in Asian Indians.


METHODS
The study comprised of 1193 normal glucose tolerant (NGT) subjects and 1018 subjects with type 2 diabetes, aged >/=20 years with an average body mass index of 23.7+/-4.6 and 25.3+/-4.2 kg/m(2), respectively. The subjects were unrelated and randomly selected from the Chennai Urban Rural Epidemiology Study (CURES), a population-based study in Chennai in southern India. The G1057D polymorphism of the IRS-2 gene was genotyped using PCR-RFLP assay.


RESULTS
The genotype frequency of the IRS-2 G1057D polymorphism was significantly different between the NGT and type 2 diabetic groups (P=0.0007) in the total study subjects and among the obese subjects (P=0.00007). Logistic regression analysis showed that the DD genotype showed an increased susceptibility to diabetes with an odds ratio (adjusted for age and sex) of 2.19 (95% CI: 1.34-3.57, P=0.002) when compared to the GG+GD genotype, among the obese subjects, but not in non obese subjects. In order to explore possible interaction with obesity, logistic regression analysis was performed and the coefficient corresponding to the interaction parameter (genotype x obesity) was significant (P=0.0001).


CONCLUSIONS
In Asian Indians, the DD genotype increases susceptibility to type 2 diabetes by interacting with obesity.
Bodhini
D
D
Madras Diabetes Research Foundation and Dr Mohan's Diabetes Specialities Centre, Gopalapuram, Chennai, India.
Radha
V
V
Deepa
R
R
Ghosh
S
S
Majumder
P P
PP
Rao
M R S
MR
Mohan
V
V
D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D007194:India / Q000453:epidemiology; D007328:Insulin / Q000235:genetics; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D012423:Rural Health; D015398:Signal Transduction / Q000235:genetics
C526297:IRS2 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins