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  • Title: Association of maternal and fetal MTHFR A1298C polymorphism with the risk of pregnancy loss: a study of an Indian population and a meta-analysis.
    Author: Nair RR, Khanna A, Singh R, Singh K.
    Journal: Fertil Steril; 2013 Apr; 99(5):1311-1318.e4. PubMed ID: 23357458.
    Abstract:
    OBJECTIVE: To study the genetic association between methylenetetrahydrofolate reductase (MTHFR) A1298 polymorphism and recurrent pregnancy loss (RPL). DESIGN: Prospective case-control study, systematic review, and meta-analysis using an electronic database up to July 27, 2012. SETTING: Meta-analysis of four studies on RPL and three studies on spontaneously aborted embryos, including the present study. PATIENT(S): A total of 129 RPL patients and 202 healthy control women with successful pregnancy were analyzed including 40 spontaneously aborted embryos and 40 aborted embryos as control samples. For meta-analysis, 1,080 case and 709 control subjects were included of RPL and 375 case and 384 control samples of spontaneously aborted embryos. INTERVENTION(S): Blood was collected by peripheral venous punctures, and spontaneously aborted embryos were collected by curettage or manual vacuum aspiration. Meta-analysis was done on the basis of heterogeneity of the studies. MAIN OUTCOME MEASURE(S): Genotyping was done by polymerase chain reaction (PCR)-restriction-fragment-length polymorphism (RFLP). DNA sequencing was used to ascertain PCR-RFLP results. Age-adjusted odds ratios were calculated by logistic regression analysis. Meta-analysis on this polymorphism was conducted to support our findings. RESULT(S): We found that presence of rare allele "C" and heterozygous and rare homozygous genotypes significantly increased the risk of RPL. No significant change in the fetal MTHFR A1298C genotype frequency was observed, regardless of chromosomal integrity. Meta-analysis of A1298C polymorphism on both RPL and in spontaneously aborted embryos showed significantly increased risk in the carriers of AC and CC genotypes. CONCLUSION(S): The data of the present study clearly suggests that MTHFR A1298C polymorphism is a genetic risk factor for pregnancy loss.
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