A novel association of a polymorphism in the first intron of adiponectin gene with type 2 diabetes, obesity and hypoadiponectinemia in Asian Indians.
Adiponectin is an adipose tissue specific protein that is decreased in subjects with obesity and type 2 diabetes. The objective of the present study was to examine whether variants in the regulatory regions of the adiponectin gene contribute to type 2 diabetes in Asian Indians. The study comprised of 2,000 normal glucose tolerant (NGT) and 2,000 type 2 diabetic, unrelated subjects randomly selected from the Chennai Urban Rural Epidemiology Study (CURES), in southern India. Fasting serum adiponectin levels were measured by radioimmunoassay. We identified two proximal promoter SNPs (-11377C-->G and -11282T-->C), one intronic SNP (+10211T-->G) and one exonic SNP (+45T-->G) by SSCP and direct sequencing in a pilot study (n = 500). The +10211T-->G SNP alone was genotyped using PCR-RFLP in 4,000 study subjects. Logistic regression analysis revealed that subjects with TG genotype of +10211T-->G had significantly higher risk for diabetes compared to TT genotype [Odds ratio 1.28; 95% Confidence Interval (CI) 1.07-1.54; P = 0.008]. However, no association with diabetes was observed with GG genotype (P = 0.22). Stratification of the study subjects based on BMI showed that the odds ratio for obesity for the TG genotype was 1.53 (95%CI 1.3-1.8; P < 10(-7)) and that for GG genotype, 2.10 (95% CI 1.3-3.3; P = 0.002). Among NGT subjects, the mean serum adiponectin levels were significantly lower among the GG (P = 0.007) and TG (P = 0.001) genotypes compared to TT genotype. Among Asian Indians there is an association of +10211T-->G polymorphism in the first intron of the adiponectin gene with type 2 diabetes, obesity and hypoadiponectinemia.
Vimaleswaran
Karani S
KS
Madras Diabetes Research Foundation, Dr. Mohan's Diabetes Specialities Centre, WHO Collaborating Centre for Diabetes and ICMR Advanced Centre for Genomics of Diabetes, Chennai, India.
Radha
Venkatesan
V
Ramya
Kandaswamy
K
Babu
Hunsur Narayan Sathish
HN
Savitha
Nageshappa
N
Roopa
Venkataramaiah
V
Monalisa
Dhar
D
Deepa
Raj
R
Ghosh
Saurabh
S
Majumder
Partha P
PP
Rao
M R Sathyanarayana
MR
Mohan
Viswanathan
V
D052242:Adiponectin / Q000097:blood / Q000172:deficiency / Q000235:genetics; D000328:Adult; D044466:Asian People / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D005820:Genetic Testing; D006801:Humans; D007194:India; D007438:Introns; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
C499918:ADIPOQ protein, human; D052242:Adiponectin