中华劳动卫生职业病杂志
中華勞動衛生職業病雜誌
중화노동위생직업병잡지
CHINESE JOURNAL OF INDUSTRIAL HYGIENE AND OCCUPATIONAL DISEASES
2011年
7期
481-486
,共6页
金如锋%万俊香%顾寿永%孙品%张忠彬%金锡鹏%夏昭林
金如鋒%萬俊香%顧壽永%孫品%張忠彬%金錫鵬%夏昭林
금여봉%만준향%고수영%손품%장충빈%금석붕%하소림
苯%中毒%多态性,单核苷酸%模型,统计学
苯%中毒%多態性,單覈苷痠%模型,統計學
분%중독%다태성,단핵감산%모형,통계학
Benzene%Poisoning%Polymorphisms,single nucleotiede%Models,statistical
目的 研究多种代谢酶基因多态性与慢性苯中毒的关联.方法 采用病例-对照研究,以152名苯中毒工人为病例组,152名接触苯而没有中毒表现的工人为对照组.应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)、测序等技术检测CYP2E1等13个基因的30个单核苷酸多态性(SNP).Logistic回归模型分析主效应和2阶交互作用,多因子降维法分析高阶交互作用.结果 logistic回归分析表明,控制了性别、吸烟、饮酒、苯接触强度的影响后,GSTP1 rs947894、CYP1A1rs4646903、CYP2D6 rs1065852、CYP2D6 rs1135840有主效应(P<0.05).EPHX1 rs1051740可能有主效应(P=0.06).GSTP1 rs947894与饮酒有交互作用;CYP2E1 rs3813867和EPHX1 rs3738047无主效应,但有交互作用;EPHX1 rs3738047与饮酒也有交互作用.未发现其他SNP与慢性苯中毒的关联.多因子降维法模型发现了1个联合作用最强的3阶交互作用,即CYP1A1 rs4646903、CYP2D6 rs1065852、CYP2D6rs1135840的3因子组合.结论 基因-基因、基因-环境交互作用是影响个体慢性苯中毒遗传易感性的重要方式.
目的 研究多種代謝酶基因多態性與慢性苯中毒的關聯.方法 採用病例-對照研究,以152名苯中毒工人為病例組,152名接觸苯而沒有中毒錶現的工人為對照組.應用聚閤酶鏈反應-限製性片段長度多態性(PCR-RFLP)、測序等技術檢測CYP2E1等13箇基因的30箇單覈苷痠多態性(SNP).Logistic迴歸模型分析主效應和2階交互作用,多因子降維法分析高階交互作用.結果 logistic迴歸分析錶明,控製瞭性彆、吸煙、飲酒、苯接觸彊度的影響後,GSTP1 rs947894、CYP1A1rs4646903、CYP2D6 rs1065852、CYP2D6 rs1135840有主效應(P<0.05).EPHX1 rs1051740可能有主效應(P=0.06).GSTP1 rs947894與飲酒有交互作用;CYP2E1 rs3813867和EPHX1 rs3738047無主效應,但有交互作用;EPHX1 rs3738047與飲酒也有交互作用.未髮現其他SNP與慢性苯中毒的關聯.多因子降維法模型髮現瞭1箇聯閤作用最彊的3階交互作用,即CYP1A1 rs4646903、CYP2D6 rs1065852、CYP2D6rs1135840的3因子組閤.結論 基因-基因、基因-環境交互作用是影響箇體慢性苯中毒遺傳易感性的重要方式.
목적 연구다충대사매기인다태성여만성분중독적관련.방법 채용병례-대조연구,이152명분중독공인위병례조,152명접촉분이몰유중독표현적공인위대조조.응용취합매련반응-한제성편단장도다태성(PCR-RFLP)、측서등기술검측CYP2E1등13개기인적30개단핵감산다태성(SNP).Logistic회귀모형분석주효응화2계교호작용,다인자강유법분석고계교호작용.결과 logistic회귀분석표명,공제료성별、흡연、음주、분접촉강도적영향후,GSTP1 rs947894、CYP1A1rs4646903、CYP2D6 rs1065852、CYP2D6 rs1135840유주효응(P<0.05).EPHX1 rs1051740가능유주효응(P=0.06).GSTP1 rs947894여음주유교호작용;CYP2E1 rs3813867화EPHX1 rs3738047무주효응,단유교호작용;EPHX1 rs3738047여음주야유교호작용.미발현기타SNP여만성분중독적관련.다인자강유법모형발현료1개연합작용최강적3계교호작용,즉CYP1A1 rs4646903、CYP2D6 rs1065852、CYP2D6rs1135840적3인자조합.결론 기인-기인、기인-배경교호작용시영향개체만성분중독유전역감성적중요방식.
Objective To explore the association of polymorphisms of metabolizing enzyme genes with chronic benzene poisoning(CBP) comprehensively by case-control design. Methods 152 CBP patients and 152 workers occupationally exposed to benzene without poisoning manifestations were investigated. 30single nucleotide polymorphisms (SNPs) in 13 genes such as CYP2E1 were tested by PCR-RFLP, sequencing approaches. Logistic regression model was used to detect main effects and 2-order interaction effects of gene and/or environment. Multifactor dimensionality reduction (MDR) was used to detect high-order gene-gene or gene-environment interactions. Results Based on logistic regression, the main effects of G57P7rs947894,EPHX1 rs1051740, CYP1A1 rs4646903, CYP2D6 rs1065852 and rs1135840 were found to be significant (P<0.05) while the confounding factors of sex, cigarette smoking, alcohol consumption and the intensity of benzene exposure were controlled. EPHX1 rs1051740 might be associated with CBP (P=0.06). There existed 3types of interactions were as followed: interactions of GSTP1 rs947894 with alcohol consumption, CYP2E1rs3813867 with EPHX1 rs3738047, EPHX1 rs3738047 with alcohol consumption(P<0.05), while the main effects of CYP2E1 rs3813867 and EPHX1 rs3738047 were not significant (P>0.05). The other SNPs did not show any significant associations with CBP. According to MDR, a 3-order interaction with the strongest combined effect was found, i.e. the 3-factor combination of CYP1A1 rs4646903, CYP2D6 rs1065852 and CYP2D6rs1135840. Conclusion Gene-gene, gene-environment interactions are important mechanism to genetic susceptibility of CBP.