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.
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Abbreviations
- ADIPOQ :
-
adiponectin gene
- BMI:
-
body mass index
- CEU:
-
Centre d’Etude du Polymorphisme Humain Utah
- DELFIA:
-
dissociation-enhanced lanthanide fluorescence immunoassay
- DEXA:
-
dual-emission X-ray absorption
- DMEM:
-
Dulbecco’s modified Eagle’s medium
- DZ:
-
dizygous
- ELISA:
-
enzyme-linked immunosorbent assay
- GEE:
-
generalised estimating equations
- HGVbase:
-
human genome variation database
- LD:
-
linkage disequilibrium
- MAF:
-
minor allele frequency
- MZ:
-
monozygous
- NCBI:
-
National Center for Biotechnology Information
- QTL:
-
quantitative trait locus
- SNP:
-
single nucleotide polymorphism
- TDT:
-
transmission disequilibrium test
- tSNP:
-
tagging SNP
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Acknowledgments
This work was funded by the British Heart Foundation Project grant No. PG/04/028 and Wellcome Trust project grant number 073142. The Twin Research and Genetic Epidemiology Unit received support from the Wellcome Trust, Arthritis Research Campaign, the Chronic Disease Research Foundation and the European Union 5th Framework Programme Genom EU twin no. QLG2-CT-2002-01254 and EuroClot project LSHM-CT-2004-005268.
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Kyriakou, T., Collins, L.J., Spencer-Jones, N.J. et al. Adiponectin gene ADIPOQ SNP associations with serum adiponectin in two female populations and effects of SNPs on promoter activity. J Hum Genet 53, 718–727 (2008). https://doi.org/10.1007/s10038-008-0303-1
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DOI: https://doi.org/10.1007/s10038-008-0303-1
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