The methylenetetrahydrofolate reductase c.c.677 C>T and c.c.1298 A>C polymorphisms in reproductive failures: Experience from an RSA and RIF study on a Polish population

Abstract

Almost 1600 individuals from the Polish population were recruited to this study. Among them 319 were fertile couples, 289 were recurrent spontaneous abortion (RSA) couples, and 131 were in the group of recurrent implantation failure (RIF) following in vitro fertilization. The aim of this study was to evaluate the MTHFR c.c.677 C>T and c.c.1298 A>C polymorphisms’ association with RSA and RIF. We used PCR-RFLP with HinfI (677 C>T) and MboII (1298 A>C) digestion. We observed a protective effect of the female AC genotype (OR = 0.64, p = 0.01) and the C allele (AC+CC genotypes; OR = 0.65, p = 0.009) against RSA. Moreover, 1298 AA/677 CT women were more frequent in RSA (31.14%) and RIF (25.20%) groups in comparison to fertile women (22.88%), although this difference was significant only in the case of RSA (p = 0.022, OR = 1.52). Male combined genotype analysis revealed no association with reproductive failure of their partners. Nevertheless, the female/male combination AA/AC of the 1298 polymorphism was more frequent in RSA couples (p = 0.049, OR = 1.49). However, the significant results became insignificant after Bonferroni correction. In addition, analysis of haplotypes showed significantly higher frequency of the C/C haplotype (1298 C/677 C) in the female control group than in the female RSA group (p = 0.03, OR = 0.77). Moreover, the association between elevated homocysteine (Hcy) level in plasma of RSA and RIF women and MTHFR polymorphisms was investigated but did not reveal significant differences. In conclusion, for clinical practice, it is better to check the homocysteine level in plasma and, if the Hcy level is increased, to recommend patients to take folic acid supplements rather than undergo screening of MTHFR for 1298 A>C and 677 C>T polymorphisms.

The Effects of Polymorphisms in One-carbon Metabolism Genes on Manifestation of Ichthyosis Vulgaris

“…It is known that various genotypes for the MTHFR, MTR, and MTRR genes are related to cardiovascular, endocrine, reproductive disorders, certain cancer types, etc. [38], [56], [57], [58], [59], [60], [61], [62], [63], [64], [65], [66], [67], [68].…”

Decreased Production of TNF-α and IL-6 Inflammatory Cytokines in Non-Pregnant Idiopathic RPL Women Immunomodulatory Effect of Sildenafil Citrate on the Cellular Response of Idiopathic RPL Women

“…However, 22 patients (aged 36.70 ± 4.48) with unexplained RPL were finally included in the study group. Recurrent pregnancy loss was defined according to the American Society for Reproductive Medicine (ASRM) guideline as two or more consecutive spontaneous miscarriages before the 20th week of gestation [ 23 , 24 ]. Complete medical, surgical and social histories were obtained in all cases.…”

“…All the women were treated according to guidelines and previous publications. Despite the optimized treatment, they experienced another obstetric failure [ 23 ]. Table 1 showed the characteristics of the study and control group.…”

“…Therefore, sildenafil citrate is currently applied for the treatment of such intragestational complications as intrauterine growth restriction (IUGR) [ 6 , 17 , 18 , 19 ], low birth weight [ 5 ], preeclampsia or idiopathic recurrent pregnancy loss (RPL) [ 5 , 7 , 19 , 20 , 21 , 22 ]. Some experiments conducted on animal models, where SC was orally administered, suggested that SC might decrease IL-1, and TNF-α in the placenta of pregnant mice [ 23 , 24 ]. Some authors reported a gender-specific action of sildenafil on immune cells, where SC diminished IL-2 and IL-6 production in the serum of female mice [ 25 ].…”

Independent, Diplotype and Haplotype Association Analyses of the Selected MTHFR SNPs with the Risk of Breast Cancers in a South-Asian Population

“…These variants affect its enzymatic activity. The function is reduced by almost 30% for the MTHFR 677C/T variation, while there is almost 60% decrease due to MTHFR 1298A/C polymorphism [12]. The 677T-variant results in the substitution of alanine with valine (Ala222Val).…”