Association of MTHFR rs1801133, PEMT rs4244593, CHKA rs7928739, VNTRs IL-1RN intron 2 and NOS3 intron 4 polymorphisms with unexplained intrauterine fetal death in Bangladeshi population

Abstract

This case-control study aimed to analyze interaction between increased risk of Intrauterine Fetal Death in Bangladeshi pregnant women and Single Nucleotide Polymorphism (SNP) of MTHFR (rs1801133), PEMT (rs4244593), CHKA (rs7928739), IL-1RN (intron 2 VNTR), and NOS3 (intron 4 VNTR). This study comprised 62 cases of IUFD and 64 controls, employed PCR/RFLP technique for MTHFR, PEMT, and CHKA gene, and only real-time PCR for IL1RN and NOS3 to observe repeat numbers. Compared to homozygous wild type (C/C) variant, heterozygous (C/A) and homozygous mutant (A/A) genotypes have shown increased risk (OR=3.18; 95% CI–1.02-9.91; p=0.04; OR=3.30; 95% Cl=0.98–11.07; p=0.05) of IUFD in PEMT analysis. However, the PEMT C/A and A/A genotypes were found to be associated with IUFD risk, in cases with no previous use of birth control (OR=0.27; 95% CI=0.08-0.92; p=0.04 and OR=0.02; 95% CI=0.06–0.79; p=0.02 respectively). IL1RN (Allele b/b) exhibited increased risk for IUFD when interacted with PEMT (A/A) genotype by 2 folds (OR=2; 95% CI=0.15–26.73; p=0.05). The genotypes of CHKA did not show any significant increase in IUFD risk. Interestingly, MTHFR and NOS3 manifested uniform distribution among cases and controls suggesting no association with IUFD risk in the Bangladeshi population.