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

Theodosios Kyriakou, Laura J. Collins, Nicola J. Spencer-Jones, Claire Malcolm, Xiaoling Wang, Harold Snieder, Ramasamyiyer Swaminathan, Keith A. Burling, Deborah J. Hart, Tim D. Spector, Sandra D. O'Dell

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)718-727
Number of pages10
JournalJournal of Human Genetics
Volume53
Issue number8
DOIs
StatePublished - Aug 1 2008

Keywords

  • Adiponectin
  • Gene transfection
  • Genetic epidemiology
  • Metabolic syndrome
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Adiponectin gene ADIPOQ SNP associations with serum adiponectin in two female populations and effects of SNPs on promoter activity'. Together they form a unique fingerprint.

  • Cite this

    Kyriakou, T., Collins, L. J., Spencer-Jones, N. J., Malcolm, C., Wang, X., Snieder, H., Swaminathan, R., Burling, K. A., Hart, D. J., Spector, T. D., & O'Dell, S. D. (2008). Adiponectin gene ADIPOQ SNP associations with serum adiponectin in two female populations and effects of SNPs on promoter activity. Journal of Human Genetics, 53(8), 718-727. https://doi.org/10.1007/s10038-008-0303-1