title: Transcription Factor-7-Like 2 Gene Variants Affect the Metabolic Phenotypes of Polycystic Ovary Syndrome.
abstract: BACKGROUND
  Polycystic ovary syndrome (PCOS) is a common endocrinopathy, which shares genetic features with type 2 diabetes mellitus (T2DM). Insofar as transcription factor 7-like 2 (TCF7L2) is consistently replicated T2DM susceptibility locus, this study evaluates whether common TCF7L2 variants are associated with PCOS and related metabolic features.
  
  
  METHODS
  The association between TCF7L2 rs4506565, rs7903146, rs12243326, and rs12255372 SNPs and PCOS was tested in 242 women with PCOS and in 236 control women.
  
  
  RESULTS
  The allelic distribution of rs4506565, rs7903146, rs12243326, and rs12255372 TCF7L2 variants was not significantly different between women with PCOS and control women. The genotype distribution of the 4 TCF7L2 loci was comparable between PCOS cases and controls, irrespective of the genetic analysis model used (additive, dominant, recessive). Carriage of rs4506565 minor allele correlated with free insulin and homeostasis model assessment of insulin resistance, while the presence of rs12243326 and rs12255372 minor allele correlated with waist changes. Four-locus (rs4506565-rs7903146, rs12243326, and rs12255372) haplotype analysis identified PCOS-susceptible (ACTG) and -protective (TTTG) haplotypes, which remained significant after controlling for multiple comparisons and for key covariates.
  
  
  CONCLUSIONS
  Although individual TCF7L2 variants were not associated with the presence of PCOS in Bahraini women, specific TCF7L2 haplotypes were identified, which were both positively and negatively associated with PCOS.
authors.affiliation: Department of Medical Biochemistry, Arabian Gulf University, Manama, Bahrain.
authors.forename: Emily
authors.initials: E
authors.lastname: Gammoh
authors.forename: Naeema A
authors.initials: NA
authors.lastname: Mahmood
authors.forename: Samira
authors.initials: S
authors.lastname: Madan
authors.forename: Bashayer H
authors.initials: BH
authors.lastname: Ebrahim
authors.forename: Fekria E
authors.initials: FE
authors.lastname: Mustafa
authors.forename: Wassim Y
authors.initials: WY
authors.lastname: Almawi
mesh_terms: D000328:Adult; D000483:Alleles; D001445:Bahrain; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics*; D010641:Phenotype; D011085:Polycystic Ovary Syndrome / Q000235:genetics* / Q000378:metabolism*; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics* / Q000378:metabolism; D055105:Waist Circumference / Q000235:genetics*
chemical_list: D007328:Insulin; D058118:Transcription Factor 7-Like 2 Protein