TY - JOUR
T1 - Adiponectin gene ADIPOQ SNP associations with serum adiponectin in two female populations and effects of SNPs on promoter activity
AU - Kyriakou, Theodosios
AU - Collins, Laura J.
AU - Spencer-Jones, Nicola J.
AU - Malcolm, Claire
AU - Wang, Xiaoling
AU - Snieder, Harold
AU - Swaminathan, Ramasamyiyer
AU - Burling, Keith A.
AU - Hart, Deborah J.
AU - Spector, Tim D.
AU - O'Dell, Sandra D.
PY - 2008/8
Y1 - 2008/8
N2 - 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 × 10-4 to 1.40 × 10-2). Associations with all except +3228 C/T were replicated in the Twins UK cohort (Ps = 3.19 × 10-9 to 6.00 × 10-3). In Chingford subjects, the 12 most common 8-SNP haplotypes (frequency 1.90%) explained 2.85% (p = 5.00 × 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 × 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.
AB - 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 × 10-4 to 1.40 × 10-2). Associations with all except +3228 C/T were replicated in the Twins UK cohort (Ps = 3.19 × 10-9 to 6.00 × 10-3). In Chingford subjects, the 12 most common 8-SNP haplotypes (frequency 1.90%) explained 2.85% (p = 5.00 × 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 × 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.
KW - Adiponectin
KW - Gene transfection
KW - Genetic epidemiology
KW - Metabolic syndrome
KW - Single nucleotide polymorphism
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U2 - 10.1007/s10038-008-0303-1
DO - 10.1007/s10038-008-0303-1
M3 - Article
C2 - 18523726
AN - SCOPUS:48549102383
SN - 1434-5161
VL - 53
SP - 718
EP - 727
JO - Journal of Human Genetics
JF - Journal of Human Genetics
IS - 8
ER -