Adiponectin gene ADIPOQ SNP associations with serum adiponectin in two female populations and effects of SNPs on promoter activity.
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.
Kyriakou
Theodosios
T
Nutritional Sciences Division, King's College London, Franklin-Wilkins Building, London, SE1 9NH, UK.
Collins
Laura J
LJ
Nutritional Sciences Division, King's College London, Franklin-Wilkins Building, London, SE1 9NH, UK.
Spencer-Jones
Nicola J
NJ
Nutritional Sciences Division, King's College London, Franklin-Wilkins Building, London, SE1 9NH, UK.
Malcolm
Claire
C
Nutritional Sciences Division, King's College London, Franklin-Wilkins Building, London, SE1 9NH, UK.
Wang
Xiaoling
X
Georgia Prevention Institute, Department of Pediatrics, Medical College of Georgia, Augusta, GA, USA.
Snieder
Harold
H
Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.|Twin Research and Genetic Epidemiology Unit, King's College London, St Thomas' Hospital Campus, London, UK.
Swaminathan
Ramasamyiyer
R
Department of Clinical Chemistry, St Thomas' Hospital, King's College London, London, UK.
Burling
Keith A
KA
Department of Clinical Biochemistry, Cambridge University Hospitals NHS Trust, Cambridge, UK.
Hart
Deborah J
DJ
Twin Research and Genetic Epidemiology Unit, King's College London, St Thomas' Hospital Campus, London, UK.
Spector
Tim D
TD
Twin Research and Genetic Epidemiology Unit, King's College London, St Thomas' Hospital Campus, London, UK.
O'Dell
Sandra D
SD
Nutritional Sciences Division, King's College London, Franklin-Wilkins Building, London, SE1 9NH, UK. sandra.odell@kcl.ac.uk.
D041721:3T3-L1 Cells; D052242:Adiponectin / Q000097:blood* / Q000235:genetics*; D000368:Aged; D000483:Alleles; D000818:Animals; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D051379:Mice; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016032:Randomized Controlled Trials as Topic
D052242:Adiponectin