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

Palep-Singh, M.; Picton, H.M.; Yates, Z.R.; Barth, J.H.; Balen, A.H.

doi:10.1016/j.ejogrb.2007.12.015

« Previous Next »European Journal of Obstetrics & Gynecology and Reproductive Biology
Volume 138, Issue 2 , Pages 180-186, June 2008

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

M. Palep-Singh
- Department of Gynaecology, Saint Mary's University Teaching Hospital, CMMC NHS Trust, Hathersage Road, Manchester, M13 0JH, UK
- Corresponding author at: Reproductive Medicine and Surgery, Department of Gynaecology, Saint Mary's University Teaching Hospital, CMMC NHS Trust, Hathersage Road, Manchester M13 0JH, UK. Tel.: +441612766358.
H.M. Picton
- Reproduction & Early Development Research Group, Faculty of Medicine and Health, University of Leeds, D Floor Clarendon Wing, Belmont Grove, Leeds LS2 9NS, UK
Z.R. Yates
- Reproduction & Early Development Research Group, Faculty of Medicine and Health, University of Leeds, D Floor Clarendon Wing, Belmont Grove, Leeds LS2 9NS, UK
J.H. Barth
- Department of Chemical Pathology & Biochemistry, Leeds General Infirmary, Leeds LS2 9NS, UK
A.H. Balen
- Reproductive Medicine Unit, Leeds Teaching Hospitals NHS Trust, C Floor Clarendon Wing, Belmont Grove, Leeds LS2 9NS, UK

Received 9 March 2007; received in revised form 13 November 2007; accepted 27 December 2007. published online 18 February 2008.

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.

Study design

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.

Keywords: Polycystic ovary syndrome (PCOS), Plasma homocysteine (Hcy), Methionine synthase gene (MTR 2756A>G), Folate