title: Plasma homocysteine concentrations and the single nucleotide polymorphisms in the methionine synthase gene (MTR 2756A>G): Associations with the polycystic ovary syndrome An observational study.
abstract: BACKGROUND
  Elevated plasma homocysteine (Hcy) is a recognized risk factor for cardiovascular disease (CVD) and other defects. Biochemical and genetic studies have characterized molecular determinants contributing to alter Hcy metabolism. The vitamin B12 dependent enzyme methionine synthase (MTR) regulates de novo production of methionine from homocysteine. Defects in the activity of this enzyme may possibly predispose to higher plasma Hcy concentrations.
  
  
  METHODS
  We examined the associations between plasma Hcy concentrations and a single nucleotide polymorphism (SNP) in the MTR gene (MTR 2756A>G), and plasma folate concentrations, in 71 women (Caucasian and South Asian) attending a fertility clinic. We also determined the ethnic variations in the frequencies of the 3 genotypes of the MTR 2756 A>G gene.
  
  
  RESULTS
  The frequency of the variant G allele was similar in the Caucasians and the South Asians (OR: 1.83; 95% CI: 0.79-4.23, p=0.2). The frequency was also similar in the PCOS and non-PCOS groups (OR: 0.88; 95% CI: 0.39-1.99). Plasma Hcy levels were significantly higher in women with PCOS compared with non-PCOS controls (p=0.05) and in Caucasian women with PCOS compared with Caucasian controls (p=0.04) in the presence of the MTR 2756 AA genotype (wild type). After adjusting for age, BMI, waist circumference and ethnicity, the significant predictors of plasma Hcy concentrations were plasma LDL, whole blood folate concentrations and a clinical diagnosis of PCOS.
  
  
  CONCLUSIONS
  The important predictors of plasma Hcy concentration in women of reproductive age are whole blood folate concentrations, a background of PCOS and plasma LDL concentrations. The SNP 2756 A>G in the MTR gene does not appear to influence the plasma Hcy levels.
authors.affiliation: Department of Gynaecology, Saint Mary's University Teaching Hospital, CMMC NHS Trust, Hathersage Road, Manchester, UK. singhrajpal@hotmail.com
authors.forename: M
authors.initials: M
authors.lastname: Palep-Singh
authors.forename: H M
authors.initials: HM
authors.lastname: Picton
authors.forename: Z R
authors.initials: ZR
authors.lastname: Yates
authors.forename: J H
authors.initials: JH
authors.lastname: Barth
authors.forename: A H
authors.initials: AH
authors.lastname: Balen
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D000328:Adult; D005260:Female; D005492:Folic Acid / Q000097:blood; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood; D010865:Pilot Projects; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies
chemical_list: D008077:Lipoproteins, LDL; D006710:Homocysteine; D005492:Folic Acid; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase