title: Genetic determinants of insulin action in polycystic ovary syndrome.
abstract: BACKGROUND
  Insulin resistance is associated with both type 2 diabetes (T2 D) and polycystic ovary syndrome (PCOS). There is an association of T2 D with several polymorphisms in candidate genes related to insulin resistance. However, there is limited information about the association of these polymorphisms with PCOS.
  
  
  METHODS
  57 non-diabetic women with PCOS and a control group of 567 healthy non-diabetic women underwent an oral glucose tolerance test (OGTT). They were genotyped for the polymorphisms Gly972Arg in IRS-1, Gly1057Asp in IRS-2, SNP 43, 44, and 45 in CAPN10, Pro12Ala in PPAR(gamma)2, C-512 T in FOXC2, and T45 G in adiponectin.
  
  
  RESULTS
  Women with PCOS had higher 2-h blood glucose levels (6.5 +/- 0.2 vs. 6.0 +/- 0.06 mmol/l, p = 0.03) compared to control women, higher fasting insulin (79 +/- 7 vs. 53 +/- 2 pmol/l, p = 0.02), and a lower insulin sensitivity estimated from the OGTT (12.4 +/- 1.1 vs. 19.1 +/- 0.5 U, p = 0.0001). More homozygous G allele carriers of the T45 G polymorphism in the adiponectin gene were found in women with PCOS compared to controls (13.2 % vs. 2.6 %, p = 0.008). In women with PCOS, G-allele carriers had lower fasting insulin levels than TT carriers (61 +/- 9 vs. 88 +/- 10, p = 0.02) in contrast to controls (p = 0.03 for interaction genotype x PCOS). The other polymorphisms were distributed equally among women with PCOS and controls (all p > 0.5).
  
  
  CONCLUSIONS
  We found a higher prevalence of the T45 G polymorphism in the adiponectin gene in women with PCOS compared to controls. This was not associated with a more insulin resistant phenotype in PCOS, however. Other frequent polymorphisms in genes related to insulin resistance and type 2 diabetes showed no association with PCOS.
authors.affiliation: Department of Endocrinology, Metabolism and Clinical Chemistry, University of Tübingen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Haap
authors.forename: F
authors.initials: F
authors.lastname: Machicao
authors.forename: N
authors.initials: N
authors.lastname: Stefan
authors.forename: C
authors.initials: C
authors.lastname: Thamer
authors.forename: O
authors.initials: O
authors.lastname: Tschritter
authors.forename: F
authors.initials: F
authors.lastname: Schnuck
authors.forename: D
authors.initials: D
authors.lastname: Wallwiener
authors.forename: M
authors.initials: M
authors.lastname: Stumvoll
authors.forename: H-U
authors.initials: HU
authors.lastname: Häring
authors.forename: A
authors.initials: A
authors.lastname: Fritsche
mesh_terms: D052242:Adiponectin; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D005260:Female; D005838:Genotype; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D010641:Phenotype; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins