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The Tyr113His T/C rs1051740 and 'very slow' phenotype of the EPHX1 gene alters miR-26b-5p and miR-1207-5p expression in pregnancy.
Gene 2017 October 31
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)=0.67g/dl; p=0.0167], LBW [TT vs. TC+CC: MD=189.30g; 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 -1.96g/dl; p=0.0021, respectively], decreased gestational age [VS vs. F: MD=-2.14weeks; p=0.0051, respectively], and LBW [N vs. VS, VS vs. F and S vs. VS: MD=1000, -940.30 and 968.80g; 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 miR-1207-5p expression, and contributes towards low blood iron levels and 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)=0.67g/dl; p=0.0167], LBW [TT vs. TC+CC: MD=189.30g; 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 -1.96g/dl; p=0.0021, respectively], decreased gestational age [VS vs. F: MD=-2.14weeks; p=0.0051, respectively], and LBW [N vs. VS, VS vs. F and S vs. VS: MD=1000, -940.30 and 968.80g; 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 miR-1207-5p expression, and contributes towards low blood iron levels and LBW.
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