【作者】 蒋慧；

【导师】 罗红；

【作者基本信息】 中南大学 ， 临床医学， 2010， 硕士

【摘要】 研究目的：探讨人细胞色素P450酶2A6(CYP2A6)基因*1(即CYP2A6wt)、*2、*3、*4(即CYP2A6del)型基因多态性与个人吸烟行为及慢性阻塞性肺疾病(COPD)遗传易感性的关系,同时与吸烟环境危险因素进行交互作用分析,寻找COPD的易感基因,为COPD高危人群的筛选、早期防治提供可能性依据。材料和方法：采用病例-对照研究,收集COPD患者90例、健康对照者90例的晨空腹静脉血,提取全血细胞基因组DNA,采用直接测序法,检测CYP2A6基因外显子3位点碱基排列序列以确定CYP2A6*1、*2、*3、*4基因型在两组人群中的分布频率,并收集各种检查指标。年龄均数的比较采用两独立样本t检验,两组的性别、吸烟史、吸烟指数构成比及各基因型频率的比较采用x2检验,,并对有统计学意义者计算其比值比(OR)和95%可信区间(CI),以评估特殊基因型及在疾病中的危险度；并用相加模型判断吸烟和基因多态性之间的交互作用。结果：1、COPD组CYP2A6wt和CYP2A6del基因型频率分别为95.56%和4.44%,而对照组分别为85.56%和14.44%；两组间比较有显著性差异(P=0.023)；携带CYP2A6wt基因型者较携带CYP2A6del基因型者患COPD风险增加3.63倍(95%Cl=1.14-11.60,P=0.023)。2、吸烟组CYP2A6wt和CYP2A6del基因型频率分别为94.29%和5.71%,而不吸烟组分别为85.33%和14.67%；两组间比较有显著性差异(P=0.043)。3、吸烟史及吸烟指数在两组中差异有统计学意义(P=0.000)；有吸烟史与无吸烟史相比,患COPD的危险性增加6.909倍(OR=6.91,95%CI=3.35-13.52;P=0.000),且随吸烟指数的增高,患COPD的危险性显著增加(OR值逐渐增大,P=0.000)。4、吸烟并携带CYP2A6wt基因型者较吸烟但携带CYP2A6del基因型者患COPD的风险性增加12.68倍(95%Cl=1.42-113.41,P=0.011)。5、携带CYP2A6wt基因型的吸烟者较携带CYP2A6wt基因型的不吸烟者患COPD的风险性增加8.28倍(95%Cl=4.01-17.11,P=0.000)。6、吸烟指数PY≥20包年并携带CYP2A6wt基因型者较吸烟指数PY≥20包年但携带CYP2A6del基因型者患COPD的风险性增加13.68倍(95%Cl=1.44-129.85,P=0.015)。结论：1、CYP2A6基因多态性可能是COPD发病的遗传危险因素。2、CYP2A6基因多态性可能影响个人吸烟行为。3、吸烟是COPD发病的危险因素,且与CYP2A6wt基因型在COPD发生学中可能有交互作用。更多还原

【Abstract】 Object To investigate whether polymorphisms in gene for CYP 2A6 have any relations on individual smoking habit and the susceptibility to the development of COPD in order to find out the "susceptible" gene in COPD.Through the gene-smoking environment interactions analysis, we can select the high dangerous population to prevent and treat the COPD.Materials and Methods The research design was a case-control study.After collecting the peripheral blood of 90 COPD patients and 90 control subjects in Han nationality of Changsha, Hunan province in China, we extracted their genomic DNA.Direct sequencing was performed to detect CYP2A6 gene polymorphisms. We also collected the clinical and laboratorial items for the research. The data of age were analyzed by t-test, the data of sex, cigarette smoking history, smoking index, frequency of genotype between groups were analyzed by Chi-square. The statistical OR and 95%CI were calculated to evaluate the risk of the special genotype. Additive model of interaction were performed to investigate the relationship between risk factors and COPD.Results (1) The frequency of CYP2A6wt and CYP2A6del genotype was 95.56% and4.44% in COPD group and 85.56% and 14.44% in control group respectively. A highly significant difference was found between the two groups (P=0.023). And that the people who carried with CYP2A6wt genotype had a 3.63 fold increased risk of COPD than those who carried with CYP2A6del genotype (95%Cl=1.14-11.60, P=0.023). (2) The frequency of CYP2A6wt and CYP2A6del genotype was94.29% and 5.71% in smoke group and 85.33% and 14.67% in non-smoke group respectively. A significant difference was found between the two groups (P=0.043). (3) There were significant differences between two groups about cigarette smoking history and smoking index (P=0.000); Smoker had a higher risk of COPD compared with non-smoker (OR=6.91,95% Cl=3.35-13.52, P=0.000). Furthermore a significant increased risk of COPD were found in patients with higher smoke index (OR=19.4> 3.59,1.00,P=0.000).(4) The smokers who carried with CYP2A6wt genotype had a 12.68 fold increased risk of COPD than that those who carried with CYP2A6del genotype (95%Cl= 1.42-113.41, P=0.011). (5) The smokers who carried with CYP2A6wt genotype had a 8.28 fold increased risk of COPD than that nonsmokers who carried with CYP2A6wt genotype (95%Cl=4.01-17.11, P=0.000). (6) The heavy smokers (PY≥20) who carried with CYP2A6wt genotype had a 13.68fold increased risk of COPD than those who carried with CYP2A6del genotype (95%CI=1.44-129.85, P=0.015). Conclusion:(1) CYP2A6 gene polymorphisms possibly was a genetic risk factor in the incidence of COPD. (2) CYP2A6 gene polymorphisms may influence smoking habit. (3) Smoking is a important risk factor in the incidence of COPD, furthermore, smoking and CYP2A6 gene polymorphisms played a positive interactive role in the development of COPD.更多还原