Two polymorphisms in methylenetetrahydrofolate reductase gene(C677T and A1298C) frequently associated with recurrentspontaneous abortion show no association in Saudi women

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.

Association between preterm birth risk and polymorphism and expression of the DNA repair genes OGG1 and APE1 in Saudi women

Genomic instability and mutations caused by increases in oxidative stress during pregnancy can damage the fetoplacental unit and can upshot preterm birth.Oxidative damage to DNA may possibly be involved in etiology of preterm birth(PTB)which can be repaired by DNA repair gene.In the present study,we assessed the association of base excision repair gene family by analyzing the association of single nucleotide polymorphisms and genes expression in 8-oxoguanine glycosylase-1(OGG1)and apurinic-apyrimidinic endonuclease 1(APE1)genes with risk of preterm birth in Saudi women.We analyzed genotypes of four single nucleotide polymorphisms(SNPs)(rs1052133,rs293795,rs2072668 and rs2075747)in OGG1 gene and three SNPs(rs1130409,rs3136814,and rs3136817)in APE1 gene using TaqMan Genotyping assay kits in 50 pairs of preterm cases and individually matched controls.Also,gene expression level was explored by RT-PCR in 10 pairs of preterm placental tissues and individually matched normal placental tissues.Two OGG1 SNP,rs1052133(OR=0.497;c2=1.11;p=0.292)and rs2072668(OR=0.408;c2=1.90;p=0.167)and one APE1 SNP rs3136817(OR=0.458;c2=0.40;p=0.527)showed nonsignificant protective effect against PTB development.The expression of both genes under study was found lower in the PTB patients.Genotype and allele frequencies of both gene SNPs did not show any association with the risk of preterm delivery in Saudi women(P˃0.05).However,synthesis and release of OGG1 and APE1 proteins decreased in preterm placental tissues compared to term delivery reflects the probability of being one of the mechanisms leading to preterm birth.