微粒体环氧化物水解酶1和谷胱甘肽S-转移酶P1与中国北方汉族慢性阻塞性肺疾病及其肺功能表型的相关性

Genetic association of EPHX1,GSTP1 and susceptibility of chronic obstructive pulmonary disease and lung function in north Chinese Han population

目的研究微粒体环氧化物水解酶(EPHX)1和谷胱甘肽S-转移酶(GST)P1在中国北方汉族人群中对慢性阻塞性肺疾病(COPD)易感性及其肺功能表型的影响。方法 310例中国北方汉族COPD患者和203例健康对照者进行肺功能表型测定,应用等位基因特异性杂交法对EPHX1和GSTP1两个基因的13个单核苷酸多态性(SNP)位点进行基因分型。采用Logistic回归和直线回归分析分别在显性、隐性和加性遗传模型下明确13个SNPs与COPD易感性及其肺功能表型之间的关系。结果 (1)EPHX1的1个SNP位点(rs3766934)和GSTP1的1个SNP位点(rs36211088)的等位基因分布在COPD组和对照组中有明显差别(P<0.05);(2)经过年龄、性别和吸烟指数的校正,并经Bonferroni多重检验后未发现与COPD易感性显著相关的SNPs位点;(3)EPHX1的rs3766934及GSTP1的rs36211088分别与较高的第1秒用力呼气容积(FEV1)值明显相关(P_(Bon)<0.05);EPHX1上的rs3766934和rs3738040分别与较高的FEV1/用力肺活量(FVC)显著相关(P_(Bon)<0.05);(4)单体型分析发现EPHX1的2个单体型及GSTP1的1个单体型分别与COPD易感性相关(P_(specific)<0.05);EPHX1的4个单体型及GSTP1的1个单体型分别与基线FEV1和FEV1/FVC显著相关(P<0.05)。其中相关性最强的单体型中包含有前述与COPD易感和肺功能表型相关的阳性位点。结论在中国北方汉族中EPHX1和GSTP1的基因多态性可能与肺功能表型相关。

Objective To determine the association of polymorphisms in microsomal epoxide hydrolase(EPH)X1 and glutathione S-transferase(GST)P1 with the susceptibility to chronic obstructive pulmonary disease(COPD)and spirometric phenotypes in Chinese Hans.Methods 42 SNPs were genotyped from the four genes in 310 cases and 203 controls,all of which were from north China and belonged to the Han population.Genotype frequencies were compared between the cases and the controls and analyzed for statistical significance.Logistic regression and linear regression were used to determine the effects of the polymorphisms on the development of COPD and the baseline lung function,assuming dominant,recessive and additive genetic model.These analyses included age,sex and pack-years as covariates.Results There were significant differences in the genotypes and allele frequencies distributions of one SNP(rs3766934)in EPHX1 and one SNP(rs36211088)in GSTP1 between the cases and controls(P<0.05).rs3766934 in EPHX1 and rs36211088 in GSTP1 were significantly associated with the higher forced expiratory volume in one second(FEV1)after Bonferroni correction(P<0.05).rs3766934 and rs3738040 in EPHX1 were significantly associated with the higher FEV1/forced vital capacity(FVC)after Bonferroni correction(P<0.05).The haplotype analyses validated the results from single SNP analyses.Conclusions The genetic variants on EPHX1 and GSTP1 are associated with the spirometric phenotypes in Chinese Han population.