EPHX1基因及EPHX2基因多态与慢性苯中毒易感性的关系

Association of genetic polymorphism of EPHX1 and EPHX2 with risks of chronic benzene poisoning

目的探讨EPHX1基因及EPHX2基因多态与慢性苯中毒易感性的关系。方法采用病例对照研究,以268名苯中毒工人为病例组,268名接触苯而无中毒表现的工人为对照组。应用TaqMan PCR分析技术检测EPHX1基因rs2854451、rs3738047、rs2234922和rs1051741及EPHX2基因rs751141位点单核苷酸多态。结果在携带EPHX1rs373804GG基因型个体中,同时携带EPHX1rs2234922G等位基因个体慢性苯中毒的发病风险降低(P=0.02),而在携带EPHX1rs2234922AA基因型个体中,同时携带EPHX2rs751141A等位基因个体慢性苯中毒的发病风险升高(P=0.03);饮酒与EPHX1基因rs1051741多态(2χH=5.28,P=0.02)或rs2234922多态(2χH=6.71,P=0.01)存在联合作用,在饮酒人群中携带突变型个体较野生纯合型苯中毒发病危险性降低(P=0.04和P<0.01);EPHX1基因单倍型分析显示,携带AGAC等位基因组成的单倍型2个体或GAGT等位基因组成的单倍型4个体慢性苯中毒的发病风险增高(P<0.001),而携带GGGT等位基因组成的单倍型6个体或AAGT等位基因组成的单倍型10个体慢性苯中毒的发病风险降低(P<0.001)。多因素Logistic回归分析提示吸烟对慢性苯中毒发病风险具有一定的修饰作用(OR=0.313,95%CI:0.123-0.794,P=0.015)。结论EPHX1基因多态性可能与慢性苯中毒发生危险性相关,而EPHX2基因多态与慢性苯中毒易感性关系需进一步研究。

Purpose To explore the association between genetic polymorphisms in EPHX1 and EPHX2 and susceptibility to chronic benzene poisoning （CBP）. Methods A case-control study of 268 CBP patients and 268 workers occupationally exposed to benzene without poisoning manifestations was conducted. The single nucleotide polymorphisms （SNPs, rs2854451, rs3738047, rs2234922 and rs1051741） of EPHX1 gene and the SNP （rs751141） of EPHX2 gene were tested by the TaqMan PCR method. Results In the subjects carrying genotype of EPHX1 rs373804 GG, the risk of CBP decreased for the individuals with allele of EPHX1 rs2234922 G （P = 0. 02）. Alternatively, in the subjects carrying genotype of EPHX1 rs2234922 AA, the risk of CBP increased for the subjects with allele of EPHX2 rs751141A （P = 0.03）. Potential interactions were found between alcohol consumption and polymorphism of EPHX1 rs1051741 （xH^2 = 5.28, P = 0.02） or rs2234922 （xH^2 = 6. 71, P = 0.01）. Compared to individuals with EPHX1 rs1051741 CC or rs2234922 AA genotype in the drinkers group, the risk of CBP for the subjects carrying genotypes of EPHX1 rs1051741 CT ＋ TT or rs2234922 AG ＋ GG was decreased, respectively （P = 0.04, P〈0. 01）. Haplotypes analysis of polymorphisms in EPHX1 showed that the risk of CBP increased for the subjects with haplotype 2 （rs2854451-A, rs3738047-G, rs2234922-A, rs1051741-C） or haplotype 4 （rs2854451-G, rs3738047- A, rs2234922-G, rs1051741-T）, but decreased for the subjects with haplotype 6 （rs2854451-G, rs3738047-G, rs2234922-G, rs1051741-T） or haplotype 10 （rs2854451-A, rs3738047-A, rs2234922- G, rs1051741-T）, respectively. Logistic regression analysis showed that smoking may play a role in modifying the risk of chronic benzene poisoning （OR = 0.313,95% CI： 0. 123 - 0. 794, P = 0. 015 ）. Conclusions Genetic polymorphisms in EPHX1 may be associated with the risk of CBP, and further research is needed for the association between genetic polymorphisms in EPHX2 and susceptibility to CBP.