Association of the MTHFR A1298C Variant with Unexplained Severe Male Infertility

Abstract

The methylenetetrahydrofolate reductase (MTHFR) gene is one of the main regulatory enzymes involved in folate metabolism, DNA synthesis and remethylation reactions. The influence of MTHFR variants on male infertility is not completely understood. The objective of this study was to analyze the distribution of the MTHFR C677T and A1298C variants using PCR-Restriction Fragment Length Polymorphism (RFLP) in a case group consisting of 344 men with unexplained reduced sperm counts compared to 617 ancestry-matched fertile or normozoospermic controls. The Chi square test was used to analyze the genotype distributions of MTHFR polymorphisms. Our data indicated a lack of association of the C677T variant with infertility. However, the homozygous (C/C) A1298C polymorphism of the MTHFR gene was present at a statistically high significance in severe oligozoospermia group compared with controls (OR = 3.372, 95% confidence interval CI = 1.27–8.238; p = 0.01431). The genotype distribution of the A1298C variants showed significant deviation from the expected Hardy-Weinberg equilibrium, suggesting that purifying selection may be acting on the 1298CC genotype. Further studies are necessary to determine the influence of the environment, especially the consumption of diet folate on sperm counts of men with different MTHFR variants.

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

“…The frequency of the MTHFR A1298C variant allele also differs across populations, the frequency of the C allele is less frequent among Chinese than among Caucasians [20]. Lack of association between MTHFR A1298C and male infertility was observed in French, Indian, Korean and Moroccan populations [17,13,24,16]. Our results are in concordance with previous studies.…”

“…A large number of molecular epidemiological studies have been conducted to evaluate the role of the three folate-related enzyme gene (MTHFR, MTR and MTRR) polymorphisms in male infertility [11,13,[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. However, the association between polymorphism and the risk of male infertility is still controversial.…”

Association between C677T and A1298C polymorphisms of the MTHFR gene and risk of male infertility: a meta-analysis

“…The characteristics of the case-control studies included in the meta-analysis are summarized in Table 1. The genotype distributions in the controls for all studies were consistent with the HWE (Norton and Neel, 1965), except for four studies (Ravel et al, 2009;Singh et al, 2010;Gava et al, 2011;Eloualid et al, 2012). …”

“…Overall, 24 case-control articles (Bezold et al, 2001;Ebisch et al, 2003;Stuppia et al, 2003;Park et al, 2005;Lee et al, 2006;Paracchini et al, 2006;A et al, 2007;Dhillon et al, 2007;Sun et al, 2007;Ravel et al, 2009;Singh et al, 2005Singh et al, , 2010Gava et al, 2011;Liu, 2011;Qiu et al, 2011;Safarinejad et al, 2011;Eloualid et al, 2012;Vani et al, 2012;Karimian and Colagar, 2014;Li et al, 2014a,b;Mfady et al, 2014;Naqvi et al, 2014;Ni et al, 2015) were included in this meta-analysis. There were 21 studies of C677T with 4505 cases and 4024 controls, and 13 studies of A1298C with 2785 cases and 3094 controls.…”

Clinical significance of polymorphism of thiopurine methyltransferase gene in children with acute lymphoblastic leukemia during programmed therapy

“…Полиморфизм генов определяли методом анализа полиморфизма длины рестрикционных фрагментов (ПДРФ-метод), принцип которого заключается в по-лимеразной цепной реакции-амплификации интере-сующего фрагмента ДНК и его последующем расще-плении соответствующей рестриктазой [15,16].…”