title: Phosphatidylinositol 3-kinase p85alpha regulatory subunit gene PIK3R1 haplotype is associated with body fat and serum leptin in a female twin population.
abstract: OBJECTIVE
  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 p85alpha regulatory subunit gene PIK3R1 with anthropometry, leptin, body fat and insulin sensitivity in a female twin population of European extraction.
  
  
  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< or =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
  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.
authors.affiliation: Department of Clinical Developmental Sciences, St George's, University of London, London, UK.
authors.forename: Y
authors.initials: Y
authors.lastname: Jamshidi
authors.forename: H
authors.initials: H
authors.lastname: Snieder
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: M J
authors.initials: MJ
authors.lastname: Pavitt
authors.forename: T D
authors.initials: TD
authors.lastname: Spector
authors.forename: N D
authors.initials: ND
authors.lastname: Carter
authors.forename: S D
authors.initials: SD
authors.lastname: O'Dell
mesh_terms: D000273:Adipose Tissue / Q000033:anatomy & histology*; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D007527:Isoenzymes / Q000235:genetics; D020738:Leptin / Q000097:blood*; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D021122:Protein Subunits / Q000235:genetics; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic; D006113:United Kingdom
chemical_list: D001786:Blood Glucose; D007527:Isoenzymes; D020738:Leptin; D021122:Protein Subunits; D019869:Phosphatidylinositol 3-Kinases