A Haplotype-Based Correlation Study On LBW Susceptibility Gene Polymorphism And Uygur,Han Low Birth Weight

Objective:To investigate the effects of microsomal epoxide hydrolase gene(EPHX1),micro-heterodimer partner gene(SHP),cytochrome oxidase P4501A1 gene(CYP1A1)and methylenetetrahydrofolate reductase gene(MTHFR)polymorphisim on the Han and Uygur low birth weight(LBW)in Urumqi.Methods: A total of 96 single births newborns with birth weight less than 2500 g were selected as low birth group,and 208 single births newborns with birth weight were 2500-4000 g as control group from the Xinjiang Autonomous Region People's Hospital and Urumqi Maternal and Child Health Hospital by case-control study.The general information of pregnant women and newborns were recorded,neonatal umbilical cord blood were collected and DNA were extracted,EPHX1 gene His139 Arg and Ile181 Ser,SHP gene rs753658661 and rs7504,CYP1A1 gene rs1048943 and rs1799814,MTHFR gene rs1801133 locus gene polymorphisms are detected by Using wafergen high throughput capture platform for second generation sequencing technology.The sex low group and the normal group sex ratio,genotype frequency,allele frequencies compared by using Chi-square test,measurement data compared by using t test,Hardy-Weinberg balance test,linkage disequilibrium test and haplotype analysis were performed by using SHEsis online software,gene interaction analysis was performed by using GMDR software and determined the best interactive model.Gene interaction map was drawn by using MDR software and determined the interaction type.Results:(1)The SNPs of EPHX1,SHP,CYP1A1 and MTHFR genes in the control group were all in Hardy-Weinberg equilibrium(P>0.05).(2)There was no significant difference in the gestational age,age of pregnant women and sex ratio of newborns between low birth weight group and control group(P>0.05).(3)The His139 Arg site of the EPHX1 gene,rs753658661 and rs7504 sites of SHP gene,rs1048943 and rs1799814 sites of CYP1A1 gene and the rs1801133 site of the MTHFR gene were not associated with the low birth weight in Uygur and Han(P>0.05),The Ile181 Ser site of the EPHX1 gene was not associated with the low birth weight in Uygur population(P> 0.05),but was significantly related to the low birth weight in Han(P<0.05),the mutant TG heterozygous genotype [OR=0.250(0.091-0.689)] And mutated G allele [OR =0.290(0.109-0.768)] can reduce the risk of low birth weight.(4)The genotype combination of the two sites of the SHP gene and the combination of the two sites of the CYP1A1 gene were not associated with the low birth weight in Han and Uygur(P>0.05),the two genotype combinations of the EPHX1 gene were not associated with low birth weight in Uyghur(P>0.05),but significantly associated with low birth weight in Han(P<0.05).Compared with the wild genotype AA / TT,the AA / TG genotype combination could reduce the risk of low birth weight [OR=0.298(0.095-0.930)].(5)The multiple loci of EPHX1,SHP and CYP1A1 genes in Uygur and Han nationality had a certain linkage strength imbalance on each gene.Haplotype analysis showed that SHP gene haplotype and CYP1A1 gene haplotype were not associated with Uygur and Han low birth weight.The EPHX1 gene haplotype was not associated with Uygur low birth weight(P>0.05),but associated with Han low birth weight.A-G haplotype reduced the risk of low birth weight [OR=0.316(0.117-0.852)].(6)MDR analysis showed that the Ile181 Ser locus of EPHX1 gene and the rs1048943 locus of CYP1A1 gene had antagonistic effect(P<0.05),the risk of low birth weight was significantly reduced in the low risk group which consisted of the TG heterozygous genotype of the Ile181 Ser mutation and the CC homozygous genotype of the rs1048943 mutation [OR = 0.259(0.118-0.570),P <0.01].Conclusion:(1)The EPXH1,SHP,CYP1A1 and MTHFR gene polymorphisms are have different effects on the occurrence of low birth weight in Han and Uyghur.(2)The SHP,CYP1A1 and MTHFR gene polymorphisms were not related to the low birth weight in Han and Uygur.The polymorphism of Ile181 Ser locus of EPHX1 gene was related to the low birth weight in Han nationality,but not with low birth weight n Uyghur.(3)The Ile181 Ser site of the EPHX1 gene and the rs1048943 site of the CYP1A1 gene have antagonistic effects on the development of low birth weight.Low birth weight is caused by the combination of multiple genes,so in the future study,as much as possible factores should be included in more comprehensive genetic analysis,with a view to a comprehensive understanding of the genetic causes of low birth weight,so as to low birth weight occurred to provide reference and improve the quality of newborn babies born.