MTHFR 1298A>C Substitution is a Strong Candidate for Analysis in Recurrent Pregnancy Loss: Evidence from 14,289 Subjects

• Published in: Reproductive sciences (Thousand Oaks, Calif.) Vol. 29; no. 4; pp. 1039 - 1053
• Main Authors: Mehta, Poonam, Vishvkarma, Rahul, Singh, Kiran, Rajender, Singh
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.04.2022
• Subjects: Abortion, Habitual - genetics; Asians - genetics; Embryology; Female; Genetic Predisposition to Disease; Genotype; Humans; Medicine; Medicine & Public Health; Methylenetetrahydrofolate Reductase (NADPH2) - genetics; Obstetrics/Perinatology/Midwifery; Polymorphism, Single Nucleotide; Pregnancy; Reproductive Medicine; Review; MTHFR; Genetic testing; Recurrent pregnancy loss; Polymorphism
• ISSN: 1933-7191; 1933-7205; 1933-7205
• DOI: 10.1007/s43032-021-00530-5

We undertook meta-analyses on MTHFR 1298A>C substitution for critically evaluating its association with recurrent pregnancy loss (RPL). MTHFR genotype data for 5888 cases and 8401 controls from 39 studies were pooled to perform this meta-analyses. Genotype data were screened, scrutinized, pooled, analysed and subjected to sensitivity analysis to carefully evaluate the association between MTHFR 1298A>C and recurrent pregnancy loss. Genetic associations were sought using dominant, recessive and co-dominant models of genetic testing with odds ratio and 95% Confidence interval (CI) as the effect measures. Further analyses were undertaken by classifying the studies into Caucasian and East Asian sub-groups. Genetic heterogeneity was tested before pooling the data across studies. For assessing publication bias, Egger’s intercept test was undertaken. We found a significant association of 1298A>C substitution with increased risk of RPL in the dominant ( P =0.000; OR = 1.58; 95% CI =1.25–1.99) as well as recessive ( P =0.000; OR = 1.66; 95% CI =1.25–2.20) models. In sub-group analysis, we observed a significant association of the polymorphism with RPL in the Caucasian populations using dominant ( P =0.000; OR = 1.98; 95% CI =1.42–2.76) and recessive ( P =0.000; OR = 2.20; 95% CI =1.49–3.24) models. However, this substitution showed no association with RPL in the East Asian populations ( P =0.149; OR = 1.187; 95% CI =0.94–1.50). MTHFR 1298A>C substitution shows association with the risk of recurrent pregnancy loss. The association is in a population-specific manner with the substitution being a strong risk factor only in the Caucasian populations.