Adiponectin gene ADIPOQ SNP associations with serum adiponectin in two female populations and effects of SNPs on promoter activity

• DOI: 10.1007/s10038-008-0303-1
• Publication Date: 2008-06-03T07:34:25Z
• Authors: Theodosios Kyriakou; Laura J. Collins; Nicola J. Spencer...; Claire Malcolm; Xiaoling Wang; Harold Snieder; Ramasamyiyer Swam...; Keith A. Burling; Deborah J. Hart; Tim D. Spector; Sandra D. O’Dell
• Keywords: 0301 basic medicine; genetic epidemiology; LINKAGE DISEQUILIBRIUM; gene transfection; BODY-FAT; 610; HAPLOTYPE; APM1 GENE; Polymorphism, Single Nucleotide; metabolic syndrome; Cohort Studies; Mice; 03 medical and health sciences; single nucleotide polymorphism; 3T3-L1 Cells; Animals; Humans; Longitudinal Studies; SUSCEPTIBILITY LOCUS; Promoter Regions, Genetic; Alleles; METABOLIC SYNDROME; PLASMA ADIPONECTIN; Aged; Randomized Controlled Trials as Topic; INSULIN-RESISTANCE; adiponectin; Middle Aged; OBESITY; CORONARY-ARTERY-DISEASE; Female; Adiponectin

Adiponectin is an insulin sensitiser in muscle and liver, and low serum levels characterise obesity and insulin resistance. Eight tagging single nucleotide polymorphisms (tSNPs) in the ADIPOQ gene and promoter were selected, and association with serum adiponectin was tested, in two independent samples of Caucasian women: the Chingford Study (n = 808, mean age 62.8 +/- 5.9 years) and Twins UK (n = 2,718, mean age 47.4 +/- 12.6 years). In the Chingford cohort, -11391 G/A, -10066 G/A (rs182052), -7734 C/A (rs16861209), +276 G/T (rs1501299) and +3228 C/T (rs1063537) were significantly associated with fasting serum adiponectin (Ps = 1.00 x 10(-4) to 1.40 x 10(-2)). Associations with all except +3228 C/T were replicated in the Twins UK cohort (Ps = 3.19 x 10(-9) to 6.00 x 10(-3)). In Chingford subjects, the 12 most common 8-SNP haplotypes (frequency 1.90%) explained 2.85% (p = 5.00 x 10(-2)) and in Twins UK subjects, the four most common 5-SNP haplotypes (frequency > 5.00%) explained 1.66% of the variance (p = 5.83 x 10(-7)). To investigate effects of -11391 G/A (rs17300539) and -11377 C/G (rs266729) on promoter activity, 1.2 kb of the ADIPOQ promoter region was cloned in a luciferase reporter plasmid, and the four haplotypes were transfected in differentiated 3T3-L1 adipocytes. No significant allelic effects on promoter activity were found.