Genetic association of ADIPOQ gene variants with type 2 diabetes, obesity and serum adiponectin levels in south Indian population.
OBJECTIVE
To investigate the genetic association of eight variants of the adiponectin gene with type 2 diabetes mellitus (T2DM), obesity and serum adiponectin level in the south Indian population.


METHODS
The study comprised of 1100 normal glucose tolerant (NGT) and 1100 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. The variants were screened by polymerase chain reaction-restriction fragment length polymorphism. Linkage disequilibrium was estimated from the estimates of haplotype frequencies.


RESULTS
Of the 8 variants, four SNPs namely, +276 G/T (rs1501299), -4522 C/T (rs822393), -11365 C/G (rs266729), and +712 G/A (rs3774261) were significantly associated with T2DM in our study population. The -3971 A/G (rs822396) and -11391 G/A (rs17300539) SNPs' association with T2DM diabetes was mediated through obesity (where the association with type 2 diabetes was lost after adjusting for BMI). There was an independent association of +276 G/T (rs1501299) and -3971 A/G (rs822396) SNPs with generalized obesity and +349 A/G (rs2241767) with central obesity. Four SNPs, -3971 A/G (rs822396), +276 G/T (rs1501299), -4522 C/T (rs822393) and Y111H T/C (rs17366743) were significantly associated with hypoadiponectinemia. The haplotypes GCCATGAAT and AGCGTGGGT conferred lower risk of T2DM in this south Indian population.


CONCLUSIONS
The adiponectin gene variants and haplotype contribute to the genetic risk towards the development of type 2 diabetes, obesity and hypoadiponectinemia in the south Indian population.
Madras Diabetes Research Foundation-ICMR Advanced Centre for Genomics of Type 2 Diabetes and Dr. Mohan's Diabetes Specialities Centre, Gopalapuram, Chennai 600086, India.
Kandaswamy
K
Ramya
Kuppuswamy Ashok
KA
Ayyappa
Saurabh
S
Ghosh
Viswanathan
V
Mohan
Venkatesan
V
Radha
D052242:Adiponectin / Q000097:blood / Q000235:genetics*; D000328:Adult; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D007194:India; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable; D012307:Risk Factors; D017422:Sequence Analysis, DNA
C499918:ADIPOQ protein, human; D052242:Adiponectin
ADIPOQ; Adiponectin; Adiponectin gene; BMI; Body Mass Index; HWE; Hardy–Weinberg Equilibrium; Hypoadiponectinemia; LD; Linkage Disequilibrium; Obesity; SNP; Single Nucleotide Polymorphism; South Indians; T2DM; Type 2 Diabetes Mellitus