Should MTHFR 1298 A>C be tested together with MTHFR 677 C>T polymorphism in women with reproductive challenges?

Methylenetetrahydrofolate reductase (MTHFR) plays a critical role in the folate metabolism. The polymorphism 677C > T of the MTHFR gene, producing thermolabile enzyme with decreased function, is widely studied and associated with many conditions. Additionally, it has been shown that another polymorphism, 1298A > C, also reduces the activity of this enzyme, although to a lesser extent. The aim of this study is to evaluate the clinical informativeness of testing both MTHFR polymorphisms. Genomic DNA, were extracted from peripheral blood of 180 female patients with pregnancy complications and 183 healthy female controls, and genotyped for MTHFR 677C > T and 1298A > C loci, using TaqMan assays. Our study found similar frequency of alleles and genotypes between two groups. Based on MTHFR 677C > T genotype, 11.7% of patients homozygous for this mutation were under the possible risk. When the position 1298 was included in the testing, 22.8% of the patients were heterozygous for both polymorphisms. Additionally, 8.9% of the patients were homozygous only for the MTHFR 1298 mutation. Although, there was no differences compared to healthy control (p > 0.05), 43% of patients were found to have elevated risk which is about four time higher than results with only MTHFR 677C > T genotyping. After obtaining information for the 677 position, testing for the second polymorphism (1298A > C) should be considered, since we have shown that it dramatically increases the rate of detection of patients who are potentially at risk for MTHFR associated conditions