神经型烟碱性胆碱能受体α4亚单位基因多态位点1860(C→T)与吸烟的相关性 以流行病学和病例调查为基础的抽样调查

Correlation of polymorphisms in the neuronal nicotinic acetylcholine receptor alpha 4 subunit gene 1860(C→T) with cigarette smoking: Sampling survey based on epidemiology and case investigation

目的:分析神经型烟碱性胆碱能受体α4亚单位基因CHRNA4多态1860(C→T)与吸烟的相关性。方法:抽取2000年北京地区流行病学调查年龄>50岁的男性健康老年人227名,2000/2002于北京宣武医院就诊的男性原发性帕金森病患者123例,共350例,在被调查者均知情同意的条件下详细调查其吸烟史包括年吸吸烟量、吸烟起时间和吸烟时间。提取所有参与者白细胞的基因组DNA,用聚合酶链反应扩增CHRNA4基因含1860(C→T)多态位点的片段,用变性高效液相色谱检测1860位基因型,测序证实变异碱基。统计分析帕金森病组与健康老年人组的1860位等位基因频率的Hardy-Weinberg吻合度检验,用SPSS9.0分析1860位变异与吸烟的相关性。结果:按意向处理分析,350例均进入结果分析。①健康人和帕金森病患者比较:227名男性健康老年人,68.3%吸烟;123例男性帕金森病患者中,35.0%吸烟,两组差异显著(P<0.001),帕金森病组与健康老年人组1860位基因型与等位基因Hardy-Weinberg检验无差异,因此将两组合并,分为吸烟与不吸烟组,总计56.9%男性吸烟。②吸烟者和不吸烟者比较:吸烟者CHRNA41860位等位基因T的频率高于不吸烟者(33.3%,23.3%,P=0.003),当前吸烟者1860T基因频率增高更为明显(35.0%,P=0.003);1860位等位T基因对年吸烟≥300包者的危险度高于年吸烟量<300包者,对吸烟持续时间≥30年者危险度高、对开始吸烟年龄<20岁者的危险度高20岁以后开始吸烟者。结论:男性中国人CHRNA4基因1860(C→T)多态与吸烟行为相关,1860等位基因T是吸烟的易感基因,并与吸烟量,吸烟持续时间和开始吸烟年龄相关;T等位基因对当前吸烟的危险度更高。

AIM: To analyze the correlation of the polymorphism of 1860(C→T) of neuronal Nicotinic Acetylcholine receptor (nAChR) α 4 subunit gene(CHRNA4) with smoking. METHODS: 227 healthy senior Chinese males who were over 50 years old based on the epidemiological study age in Beijing area in 2000 and 123 male patients with primary Parkinson's disease who diagnosed in Beijing Xuanwu Hospital from 2000 to 2002 were selected to investigate, totally 350 cases. Based on the investigators who were investigated knowing the condition and making agreement, the history of cigarette smoking was investigated in detail, including numbers of cigarette smoked per year, duration of smoking, and age when began to smoke. DNA was extracted from leukocytes of all subjects. 1860(C→T) of CHRNA4 were amplified with polymerase chain reaction (PCR) and genotypes were identified using Denaturing High Performance Liquid Chromatography (DHPLC) techniques and confirmed by sequencing. Hardy-Weinberg test were performed to allele frequencies between group of PD and healthy senior people, statistic analysis on the association of polymorphism 1860 with smoking were reached by using SPSS 9.0. RESULTS: According to intention-to-treat analysis, totally 350 cases were involved in the analysis of results. ① The comparison between healthy senior people and PD patients: There were 68.3% smokers among 227 healthy seniors, and 35.0% smokers among PD patients. There were significant difference between the two groups (P < 0.001). Since no significant difference was detected to the alleles and genotype of 1860 mutation of CHRNA4 with Hardy-Weinberg test, group of PD and healthy senior were combined to analysis the association with smoking and non-smoking group, totally 56.9% smokers. ② The comparison between smoking and non-smoking people: Allele T of 1860 was more frequent in smokers than in non-smoker (33.3% to 23.0%, P=0.003), it was more significant when the frequency of allele T of 1860 (35.0%,P=0.003); The risk ratio of allele T was higher in group which tobacco consumption was ≥300 packs per year than that in group which tobacco consumption < 300 packs. The risk was high in group which duration of smoking was ≥30 years, and the risk was high in group which began to smoke at age of < 20 years old than that after 20 years old. CONCLUSION: 1860(C→T) of CHRNA4 is associated with cigarette smoking in Chinese men, and allele T of 1860 which is the predisposing genes of smoking is associated with numbers of cigarette smoked, duration of smoking and age when began to smoke; T allele has higher risk on smoking at present.