The significance of 1793G>A polymorphism in MTHFR gene in women with first trimester recurrent miscarriages.

BACKGROUND: Recurrent miscarriages (RM) are significant social and clinical problem. One of suggested reason of RM is hyperhomocysteinemia. Polymorphic genes involved in homocysteine and folate metabolism, including 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, are considered as an important risk factors for homocysteine accumulation and modulator of RM susceptibility. Therefore the aim of this study was to evaluate the frequency of MTHFR polymorphisms (677C>T, 1298A>C, and 1793G>A) in women with recurrent miscarriages.

MATERIAL AND METHODS: We have analyzed 104 Polish women with a history of 3 or more unexplained recurrent miscarriages in the first pregnancy trimester (6-13 gestation week). The control group consisted of 169 women without obstetrical complication, any history of miscarriage and with at least one live birth in anamnesis. The investigated polymorphisms were determined by PCR/RFLP methods.

RESULTS: For MTHFR 1793G>A polymorphism we have observed significant overrepresentation of heterozygotic GA genotypes in RM group (15.38% vs. 4.14% in the controls, OR=4.21, p=0.003). For 677C>T and 1298A>C we have shown lack of significant association with RM. Nevertheless, such significant association was observed if more than one mutated MTHFR variant was present in one patient.

CONCLUSIONS: Our research indicate the possible role of MTHFR 1793G>A polymorphism in pathogenesis of RM. The noticed tendency to more frequent occurrence of haplotypes of MTHFR gene including two or three mutated alleles showed the possibility of summarized amplification of these variants effect influencing RM susceptibility.