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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

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机构: [1]哈尔滨医科大学附属第二医院神经科,黑龙江省哈尔滨市150086 [2]国家人类基因组北方研究中心,北京市,100176 [3]首都医科大学宣武医院神经内科,北京市老年病研究所神经生物研究室,北京市100053
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摘要:
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.

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第一作者机构: [1]哈尔滨医科大学附属第二医院神经科,黑龙江省哈尔滨市150086
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通讯机构: [2]国家人类基因组北方研究中心,北京市,100176 [3]首都医科大学宣武医院神经内科,北京市老年病研究所神经生物研究室,北京市100053
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