Polymorphisms in Folate-Related Enzyme Genes in Idiopathic Infertile Brazilian Men

Abstract

The aim of the study was to analyze the distribution of the methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR), and methionine synthase (MTR) polymorphisms in idiopathic infertile Brazilian men and fertile men. Case-control study comprising 133 idiopathic infertile Brazilian men with nonobstructive azoospermia ([NOA] n = 55) or severe oligozoospermia ([SO] n = 78) and 173 fertile men as controls. MTHFR C677T, A1298C, and G1793A; MTRR A66G; and MTR A2756G polymorphisms were studied by quantitative polymerase chain reaction (qPCR). The results were analyzed statistically and a P value <.05 was considered significant. Single-marker analysis revealed a significant association among MTHFR C677T polymorphism and both NOA group (P = .018) and SO group (P < .001). Considering the MTHFR A1298C, MTHFR G1793A, and MTRR A66G polymorphisms, no difference was found between NOA group and SO group. Regarding the MTR A2756G polymorphism, a significant difference was found between NOA and controls, P = .017. However, statistical analysis revealed no association between SO group and controls. Combined genotypes of 3 MTHFR polymorphisms did not identify a haplotype associated with idiopathic infertility. The combinatory analysis of the 3 polymorphisms MTHFR, MTRR, and MTR did not show difference between cases and controls. The findings suggest the MTHFR C677T and MTR A2756G polymorphisms could be an important genetic factor predisposing to idiopathic infertility in Brazilian men.

Lack of association between genetic polymorphisms in three folate-related enzyme genes and male infertility in the Chinese population

“…They found that MTHFR C677T, MTR A2756G and MTRR A66G genotypes were independently associated with male infertility [13]. Geographic variation, racial, and ethnic differences in the distribution of the polymorphisms in folate-related enzyme genes could be one of the explanations for conflicting findings [44]. Moreover, gene-nutrient/environmental and gene racial/ethnic interactions have been shown to influence the impact of MTHFR polymorphisms [45].…”

“…The single nucleotide primer extension assay consisted of 5 μL SNaPshot Multiplex Mix (Applied Biosystems), 2 μL purified PCR product and 0.8 μM of each primer in a final reaction volume of 10 μL. The following specific primers were used: rs1801131SR, 5′ -T 29 GG GGA GGA GCT GAC CAG TGA AG -3′; rs1801133SF, 5′ -T 44 AA AAG CTG CGT GAT GAT GAA ATC G -3′; rs1805087SR, 5′ -T 18 CC ACT TAC CTT GAG AGA CTC ATA ATG G -3′ and rs1801394SR, 5′ -T 17 CC ATG TAC CAC AGC TTG CTC ACA -3′. The amplification consisted of 28 cycles of 96°C for 10 s, 50°C for 5 s, and 60°C for 30 s. Then, 1 μL of SAP was added to each reaction and incubated at 37°C for 1 h followed by heat inactivation at 75°C for 15 min.…”

Individual capacity for DNA repair and maintenance of genomic integrity: a fertile ground for studies in the field of assisted reproduction

“…[79,80] Similar results have been obtained for the role of MTHFR C677T and the MTR A2756G polymorphisms in the Brazilian population. [81] The association was not confirmed for European males in population samples of approximately the same size. [82] It is possible that carriership of the T allele of MTHFR C677T may be a population-specific risk factor for male infertility.…”

Association between methionine synthase reductase A66G polymorphism and primary infertility in Chinese males

“…Lee et al (2006) reported that the frequencies of MTRR 66GG genotypes in non-obstructive infertile men, MS 2756GG genotypes in the azoospermia group, and MTRR 66GG in the OA group were higher compared with those in fertile Korean men. Gava et al (2011b) showed that MS A2756G polymorphisms may be important in the predisposition to primary infertility in Brazilian men. However, Farcas et al (2009) and Ravel et al (2009) suggested that these polymorphisms in infertile men were not significantly more common than in controls.…”