Methylenetetrahydrofolate reductase C677T and A1298C polymorphism and changes in homocysteine concentrations in women with idiopathic recurrent pregnancy losses

Because they have been described as strong risk factors for idiopathic recurrent pregnancy losses (RPLs), we assessed the association between the methylenetetrahydrofolate reductase (MTHFR) single-nucleotide polymorphisms (SNPs) C677T and A1298C and hyperhomocysteinemia in Tunisian women with idiopathic RPL. Study subjects comprised 200 patients with more than three consecutive RPLs, and 200 age-matched parous control women. C677T and A1298C SNPs were analyzed by PCR-RFLP analysis, and fasting serum homocysteine was measured with ELISA. The frequency of MTHFR 677T/T (30.0 vs 7.0%) and 1298C/C (13.5 vs 4.0%) genotypes was significantly higher in patients. While it was similar among patients and controls (P = 0.095), higher homocysteine was seen with the T/T (but not 1298A/C and 1298C/C) genotype among patients and controls compared with non-T/T carriers (P < 0.05), and in patients vs controls. Higher prevalence of MTHFR 677T/T was seen in late (P < 0.05) and early-late (P < 0.001) RPL, while higher prevalence of 1298C/C genotype was seen only in early-late RPL (P < 0.001), and the prevalence of double heterozygotes was statistically not significant between patients and controls (P = 0.10; odds ratio = 2.73). Logistic regression analysis showed that, after adjusting for all variables, homozygosity for MTHFR C677T was associated with late (P < 0.001), and combined early-late (P < 0.001), while homozygosity for A1298C was associated only with combined early-late (P = 0.026), as was secondary-level education, which was associated with early (P = 0.005), late (P = 0.026) and combined early-late (P = 0.004) abortions. Homozygosity for MTHFR C677T (late and early-late) and A1298C (early-late) are risk factor for RPLs, irrespectively of total homocysteine levels. © 2006 Society for Reproduction and Fertility.