EPHX1基因的Tyr113His T/C rs1051740及“非常缓慢”表型改变孕期miR-26b-5p和miR-1207-5p的表达。
The Tyr113His T/C rs1051740 and 'very slow' phenotype of the EPHX1 gene alters miR-26b-5p and miR-1207-5p expression in pregnancy.
作者信息
Naidoo Pragalathan, Naidoo Rajen N, Ramkaran Prithiksha, Asharam Kareshma, Chuturgoon Anil A
机构信息
Discipline of Medical Biochemistry and Chemical Pathology, Howard College Campus, University of KwaZulu-Natal, Durban, South Africa.
Discipline of Occupational and Environmental Health, University of KwaZulu-Natal, Durban, South Africa.
出版信息
Gene. 2017 Oct 30;633:71-81. doi: 10.1016/j.gene.2017.07.080. Epub 2017 Aug 5.
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.
背景
环境损伤以及微粒体环氧化物水解酶1（EPHX1）单核苷酸多态性（SNP），即Tyr113His T/C rs1051740和His139Arg A/G rs2234922，会异常改变微小RNA（miR）的表达，并与低出生体重（LBW）有关。
目的
研究孕期污染、EPHX1单核苷酸多态性和微小RNA之间的相互作用以及相关的低出生体重结局。
方法
在德班的MACE出生队列研究中招募了南非孕妇（n = 241），德班是一个工业和交通相关污染物水平较高的城市。使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对EPHX1单核苷酸多态性进行基因分型，并将其分为各自的表型，即正常（N）、缓慢（S）、非常缓慢（VS）和快速（F）。使用定量PCR测定EPHX1、miR-26b-5p、miR-193b-3p和miR-1207-5p的表达。
结果
携带Tyr113His单核苷酸多态性的母亲铁水平较低[TT与TC + CC相比：平均差异（MD）= 0.67g/dl；p = 0.0167]，出生体重低[TT与TC + CC相比：MD = 189.30g；p = 0.0067]，且EPHX1表达较低；p < 0.0001。与TT + TC组相比，CC基因型中miR-26b-5p和miR-1207-5p的表达显著更高；p < 0.0001。miR-193b-3p则呈现相反趋势；p = 0.0045。具有VS表型的母亲铁水平较低[N与VS以及VS与F相比：MD分别为2.03和-1.96g/dl；p分别为0.0021]，孕周缩短[VS与F相比：MD = -2.14周；p = 0.0051]，且出生体重低[N与VS、VS与F以及S与VS相比：MD分别为1000、-940.30和968.80g；p均< 0.0001]；F表型的EPHX1表达最高[N与F、VS与F以及S与F相比：MD分别为-1.067、-1.854和-1.379；p = 0.0002]；N表型的miR-26b-5p [N与VS相比：MD = -0.6100；p = 0.0159]和miR-1207-5p [N与VS以及VS与F相比：MD分别为-0.834和1.103；p分别为0.0007]表达较低。各表型之间miR-193b-3p的表达保持不变。
结论
rs1051740的Tyr113His T/C变异和VS表型会改变EPHX1、miR-26b-5p和miR-1207-5p的表达，并导致低血铁水平和低出生体重。
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