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.

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.

Polycystic ovary syndrome and the single nucleotide polymorphisms of methylenetetrahydrofolate reductase: a pilot observational study.

UNLABELLED: Polycystic ovary syndrome (PCOS), insulin resistance and overall mortality due to diabetes and coronary artery disease are higher in South Asians than in Caucasians. AIMS: We compared the prevalence of the C677T and A1298C single nucleotide polymorphisms in the methylenetetrahydrofolate reductase gene in South Asian and Caucasian women, its association with folate and homocysteine (Hcy) metabolism, and its relevance to future atherogenic events. METHODS AND RESULTS: 71 women were recruited for the study: South Asian PCOS (21) plus controls (9) and Caucasian PCOS (25) plus controls (16). Anthropometric and laboratory parameters were compared. South Asian PCOS women were significantly hyperandrogenic and exhibited a greater degree of insulin resistance. Caucasian PCOS women had higher plasma Hcy concentrations with a 1.9 times higher frequency of the T allele than the South Asian PCOS group. In the presence of this variant allele, plasma Hcy levels appear to be higher in both PCOS groups. The South Asians had a 1.8 times higher frequency of the C allele than the Caucasians; however, the overall frequency was comparable in the two PCOS groups. The frequency of homozygosity, i.e. TT677 and CC1298, was 7.2% and 4.9% in the Caucasians and 0% and 16.6% in the South Asian recruits, respectively. Dietary inadequacies in the South Asian women can influence their plasma folate and B12 concentrations resulting in hyperhomocysteinemia which, in combination with dyslipidaemia and insulin resistance, can lead to long-term atherogenic consequences. CONCLUSIONS: Current data suggests that the mechanisms of atherothrombosis have separate pathways in the two ethnic groups. Larger studies exploring the current theme need to be carried out in the PCOS groups to obtain adequate insight.

South Asian women with polycystic ovary syndrome exhibit greater sensitivity to gonadotropin stimulation with reduced fertilization and ongoing pregnancy rates than their Caucasian counterparts.

UNLABELLED: Polycystic ovary syndrome (PCOS) is a heterogeneous syndrome. In vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) is required for PCOS cases that are refractory to standard ovulation induction or have co-existing infertility factors in women with PCOS and Tubal factor subfertility. OBJECTIVES: Assess ethnic variations in response to IVF/ICSI treatment. STUDY DESIGN: Observational Comparative study in a University hospital fertility clinic in women with PCOS and Tubal factor subfertility. Women with PCOS (Asians: AP=104; Caucasians: CP=220) and those with tubal factor infertility seeking fertility treatment were assessed (Asians: AC=84; Caucasians: CC=200). Six hundred and eight fresh IVF or ICSI cycles using long protocol of GnRHa suppression and resulting in a fresh embryo transfer were compared. The primary endpoint was to assess the dose of gonadotropins used in the cycles. The secondary outcomes were: total number of oocytes retrieved, fertilization and ongoing clinical pregnancy rates. RESULTS: We found that the South Asian women presented at a younger age for the management of sub-fertility. An extended stimulation phase and Caucasian ethnicity showed an inverse correlation with the number of oocytes retrieved in the PCOS subgroup. Caucasian ethnicity was associated with a higher fertilization rate however increase in body mass index (BMI) and the laboratory technique of IVF appeared to have a negative impact on fertilization rates in the PCOS subgroup. Commencing down regulation on day 1 of the cycles was negatively associated with fertilization rates in the tubal group. In terms of clinical pregnancy rates, the Caucasian PCOS had a 2.5 times (95% CI: 1.25-5) higher chance of an ongoing clinical pregnancy as compared with their Asian counterpart. Also, a unit increase in the basal FSH concentration reduced the odds of pregnancy by 18.6% (95% CI: 1.8-32.6%) in the PCOS group. CONCLUSIONS: The Asian PCOS have a greater sensitivity to gonadotropin stimulation with lower fertilization and ongoing clinical pregnancy rates as compared with their Caucasian counterparts.