Abstract
Methylenetetrahydrofolate reductase (MTHFR) deficiency is the most common genetic cause of hyperhomocysteinemia, which has been implicated in the etiology of recurrent spontaneous abortion (RSA). This study was designed to investigate the association between two single nucleotide polymorphisms (SNP) (rs1801133 [C677T] and rs1801131 [A1298C]) in the MTHFR gene and RSA, in Saudis. These two SNPs were selected as these polymorphisms have a different effect on the activity and stability of the enzyme, and significantly diverse effects have been reported in relation to the association with RSA. Ethical approval was acquired from the IRB at King Saud University (KKUH), Saudi Arabia, and written informed consent was obtained from each participant. The study group comprised of 100 Saudi women with unexplained RSA and 100 age-matched controls, both attending KKUH for a routine checkup. Blood was drawn in EDTA tubes, and DNA was extracted. Genotyping was conducted using TaqMan SNP genotyping assay kits. The frequency of the T allele of C677T was 0.165 in patients and 0.17 in controls. Genotype frequencies for CC, CT and TT genotypes were 70%, 27% and 3%, respectively in RSA, and 71%, 24% and 5%, respectively, in the controls (p > 0.05). For the A1298C polymorphism, the C allele frequencies were 0.345 in patients and 0.28 in controls, while genotype frequencies for AA, AC and CC genotypes were 44%, 43%, and 13%, respectively, in patients, and 54%, 36%, and 10%, respectively, in controls (p > 0.05). The frequency of CC genotype and C allele of A1298C were higher in the patients with RSA, but not significantly, while C677T genotypes and allele frequencies did not differ between patients and controls. The results suggested that MTHFR gene polymorphisms are population-specific and may not associate with RSA in Saudi women.