Phosphatidylinositol 3-kinase p85α regulatory subunit gene PIK3R1 haplotype is associated with body fat and serum leptin in a female twin population

被引:20
作者
Jamshidi, Y.
Snieder, H.
Wang, X.
Pavitt, M. J.
Spector, T. D.
Carter, N. D.
O'Dell, S. D.
机构
[1] Kings Coll London, Nutr Food & Hlth Res Ctr, London SE1 9NH, England
[2] St Georges Univ London, Dept Clin Dev Sci, London, England
[3] Med Coll Georgia, Georgia Prevent Inst, Dept Pediat, Augusta, GA 30912 USA
[4] Kings Coll London, Twin Res & Genet Epidemiol Unit, London WC2R 2LS, England
[5] Kings Coll London, Nutr Food & Hlth Res Ctr, London SE1 9NH, England
基金
英国惠康基金;
关键词
cytokines; epidemiology; genetics; obesity; weight regulation;
D O I
10.1007/s00125-006-0388-z
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Aims/hypothesis Phosphatidylinositol 3-kinase (PI3K) couples the leptin and insulin signalling pathways via the insulin receptor substrates IRS1 and IRS2. Hence, defective activation of PI3K could be a novel mechanism of peripheral leptin or insulin resistance. We investigated associations of tagging single-nucleotide polymorphisms (tSNPs) in the PI3K p85 alpha regulatory subunit gene PIK3R1 with anthropometry, leptin, body fat and insulin sensitivity in a female twin population of European extraction. Materials and methods Eight tSNPs were genotyped in 2,778 women (mean age 47.4 +/- 12.5 years) from the St Thomas' UK Adult Twin Registry (Twins UK). Results SNP rs1550805 was associated with serum leptin (p=0.028), BMI (p=0.025), weight (p=0.019), total fat (p=0.004), total fat percentage (p=0.002), waist circumference (p=0.025), central fat (p=0.005) and central fat percentage (p=0.005). SNPs rs7713645 and rs7709243 were associated with BMI (p=0.020 and p=0.029, respectively), rs7709243 with weight, total and central fat (p=0.026, p=0.031 and p=0.023, respectively) and both SNPs with fasting glucose (p=0.003 and p=0.001, respectively) and glucose 2-h post OGTT (p=0.023 and p=0.007, respectively). Subjects with haplotype 222 (frequency 7.2%) showed higher serum leptin concentration (p=0.007) and body fat measures (p <= 0.001 for all), and those with haplotype 221 (frequency 38.7%) showed higher fasting and 2-h glucose (p=0.035 and p=0.021, respectively) compared with subjects with the most common haplotype, 111 (frequency 45.5%). Conclusions/interpretation Association of the PIK3R1 SNP rs1550805 with serum leptin and body fat may reflect a diminished ability of PI3K to signal via IRS1 or IRS2 in response to leptin.
引用
收藏
页码:2659 / 2667
页数:9
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