Background: Environmental insults and microsomal epoxide hydrolase 1 (EPHX1) single nucleotide polymorphisms (SNPs), Tyr113His T/C rs1051740 and His139Arg A/G rs2234922, aberrantly alters microRNA (miR) expression and are linked to low birthweights (LBW). Objectives: To investigate the interplay between pollution, EPHX1 SNPs and miRs during pregnancy and associated LBW outcomes. Methods: South African pregnant women (n = 241) were recruited in the MACE birth cohort study in Durban, a city with high levels of industry and traffic related pollutants. EPHX1 SNPs were genotyped using PCR-RFLP and grouped into their respective phenotypes, i.e. normal (N), slow (S), very slow (VS) and fast (F). EPHX1, miR-26b-5p, miR-193b-3p and miR-1207-5p expression were determined using quantitative PCR. Results: Mothers with the Tyr113His SNP had low iron levels [TT vs. TC + CC: mean difference (MD) = 0.67 g/ dl; p = 0.0167], LBW [TT vs. TC + CC: MD = 189.30 g; p = 0.0067], and low EPHX1 expression; p < 0.0001. miR-26b-5p and miR-1207-5p expression were significantly higher in the CC genotypes compared to TT + TC groups; p < 0.0001. The opposite trend occurred for miR-193b-3p; p = 0.0045. Mothers with the VS phenotype had low iron levels [N vs. VS and VS vs. F: MD = 2.03 and - 1.96 g/dl; p = 0.0021, respectively], decreased gestational age [VS vs. F: MD = - 2.14 weeks; p = 0.0051, respectively], and LBW [N vs. VS, VS vs. F and S vs. VS: MD = 1000, - 940.30 and 968.80 g; p < 0.0001, respectively]; F phenotype had the highest EPHX1 expression [N vs. F, VS vs. F and S vs. F: MD = - 1.067, - 1.854 and - 1.379; p = 0.0002, respectively]; and N phenotype had low miR-26b-5p [N vs. VS: MD = - 0.6100; p = 0.0159] and miR-1207-5p [N vs. VS and VS vs. F: MD = - 0.834 and 1.103; p = 0.0007, respectively] expression. miR-193b-3p expression between phenotypes remained unchanged. Conclusion: The Tyr113His T/C variant of rs1051740 and VS phenotype alters EPHX1, miR-26b-5p and miR1207-5p expression, and contributes towards low blood iron levels and LBW.
