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

Y. Jamshidi, H. Snieder, X. Wang, M. J. Pavitt, T. D. Spector, N. D. Carter, Sandra D. O'Dell

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

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 p85α 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.

Original languageEnglish (US)
Pages (from-to)2659-2667
Number of pages9
JournalDiabetologia
Volume49
Issue number11
DOIs
StatePublished - Nov 2006

Keywords

  • Cytokines
  • Epidemiology
  • Genetics
  • Obesity
  • Weight regulation

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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