Association between premature ovarian failure, polymorphisms in MTHFR and MTRR genes and serum homocysteine concentration

Abstract

This study investigated the association between premature ovarian failure (POF), MTHFR C677T/A1298C and MTRR A66G genotypes and serum homocysteine (Hcy) concentration. A prospective study was conducted in Chinese women, which included POF patients (n = 180) and controls (n = 195). Peripheral blood samples were used to determine MTHFR C677T/A1298C and MTRR A66G genotypes, and serum Hcy and sex hormone concentrations. Results showed that serum Hcy concentrations of POF patients were significantly higher than those of controls (P < 0.0001). In POF patients, serum Hcy concentrations were significantly correlated with oestradiol and FSH concentrations (r = -0.174, P = 0.037 and r = +0.238, P = 0.006, respectively). There were no significant differences in the distributions of MTHFR C677T/A1298C or MTRR A66G genotypes between the two groups. However, these genetic variants influenced serum Hcy concentrations in POF patients, especially for MTRR 66 AA/AG/GG genotypes, which were significantly correlated with the patients' Hcy concentrations (τ = 0.166, P = 0.033). These results suggest that serum Hcy concentrations in Chinese POF patients are increased and correlated with serum oestradiol/FSH concentrations. In conclusion, MTHFR C667T/A1298C and MTRR A66G genotypes are not associated with POF development, but they affect the patients' serum Hcy concentrations.

Effect of MTHFR A1298C and MTRR A66G genetic mutations on homocysteine levels in the Chinese population: a systematic review and meta-analysis

“…Of the 40 studies, 10 were excluded because of lack of genotyping data, 7 were review articles, 5 were not relevant, and 5 deviated from the Hardy-Weinberg Equilibrium (P < 0.05). Finally, 13 studies [10,12,14,[18][19][20][21][22][23][24][25][26][27] were suitable for the meta-analysis (Figure 1). …”

“…Among the 13 studies, 7 were case-control studies [12,14,[23][24][25][26][27] and 6 were cross-sectional studies. [10,[18][19][20][21][22] In addition, five manuscripts [10,12,14,[21][22] were published in English, and eight manuscripts [18][19][20][23][24][25][26][27] were published in Chinese.…”

“…Among the 13 studies, 7 were case-control studies [12,14,[23][24][25][26][27] and 6 were cross-sectional studies. [10,[18][19][20][21][22] In addition, five manuscripts [10,12,14,[21][22] were published in English, and eight manuscripts [18][19][20][23][24][25][26][27] were published in Chinese. Hcy was measured by fluorescent polarization immunoassay, [14,22,24] high-performance liquid chromatography, [10,23,27] enzymatic cycle method, [12,[19][20]26] chemiluminescence method, [18] and enzyme-linked immunosorbent assay.…”

“…[10,[18][19][20][21][22] In addition, five manuscripts [10,12,14,[21][22] were published in English, and eight manuscripts [18][19][20][23][24][25][26][27] were published in Chinese. Hcy was measured by fluorescent polarization immunoassay, [14,22,24] high-performance liquid chromatography, [10,23,27] enzymatic cycle method, [12,[19][20]26] chemiluminescence method, [18] and enzyme-linked immunosorbent assay. [25] Genotype was analyzed by fluorescence quantitative polymerase chain reaction, [12,18,26] polymerase chain reaction-restriction fragment length polymorphism, [10,14,[22][23][24][25]27] ligase detection reaction, [19] iPLEX gold chemistry, [21] and taqman-minor groove binder.…”

“…The 5-methyl-THF product donates a methyl group to Hcy in the generation of S-adenosylmethionine, a major source of methyl groups used for DNA methylation. [11] MTRR regenerates a functional methionine synthase via reductive methylation, which is associated with the Hcy transfer to methionine, [12] Two common polymorphisms of the MTHFR gene are C677T and A1298C. The MTHFR 677C→T polymorphism leads to a reduction in enzyme activity, resulting in increased concentrations of plasma Hcy and lower levels of serum folate.…”