张龙玉，闫　亮，郝书理，叶文华，张纪元，李保森，黄　昂，田辉，刘西秦，邹正升

·酒精性肝病·

乙醛脱氢酶2基因多态性与酒精性肝病患者饮酒特点和疾病发生的关系*

张龙玉，闫亮，郝书理，叶文华，张纪元，李保森，黄昂，田辉，刘西秦，邹正升

目的分析乙醛脱氢酶2（ALDH2）基因多态性与酒精性肝病（ALD）患者饮酒特点与疾病发生的关系。方法采用TaqMan荧光定量PCR法，对无血缘关系的296例健康对照者（HC）以及221例ALD患者进行ALDH2基因多态性检测，并分析其与ALD患者饮酒特征和疾病发生的关系。结果ALDH2在健康人中突变频率为31.1%（92/296），远高于欧美、非洲等国家（几乎为零），稍高于亚洲平均水平（22%）；ALDH 2*1/*1基因型频率，ALD患者组明显高于健康人[93.7%(207/221)Vs 69.0%(204/296)，OR=6.668,p<0.0001]，ALDH2*1等位基因的频率，ALD患者组亦明显高于健康人[96.8%(428/442)Vs 82.9%(491/592),OR=6.289,p<0.0001]；ALDH 2*1/*2基因型频率，ALD患者组明显低于健康人[6.3%(14/221)Vs 28.0%(83/296),OR=0.174,p<0.0001]，ALDH2*2/*2基因型频率，ALD患者组亦明显低于健康人[0%(0/221)Vs 3.0%(9/296)，OR=0.13,p<0.05]。ALDH2*2等位基因频率，ALD患者组亦明显低于健康人[3.2%（14/442）Vs 17.1%（101/592），OR=0.159,p<0.01]；ALDH2基因多态性在ALD患者疾病进程的各个阶段分布无明显统计学差异；与ALDH2*1/*1基因型相比，拥有ALDH2*2携带者基因型饮酒者在较少的总饮酒量情况下即可发生ALD（p均<0.05）。结论ALDH2*1等位基因是饮酒者发生ALD的重要危险因素，在较多饮酒量和较长时间饮酒的情况下才发生ALD；ALDH2*2等位基因可“保护”机体避免发生ALD，但饮酒者在较少饮酒量和较短饮酒时间的情况下即可发生ALD。

ALDH2；基因多态性；ALD；饮酒特征

【Abstract】Objective To explore the correlation between gene polymorphism of acetaldehyde dehydrogenase 2(ALDH2)and drinking features as well as disease onset in patients with alcoholic liver disease (ALD).Methods TaqMan fluorescent quantitation PCR was used for detecting gene polymorphism of ALDH 2 in 296 unrelated healthy controls(HC)and 221 patients with ALD.The correlation between the ALDH2 gene polymorphism and the drinking features as well as disease onset of patients with ALD was analyzed.Results Mutation frequency of ALDH2 in recruited HC was 31.1%(92/296),which was far higher than that of almost zero in Europe,America,Africa and other countries(almost zero),and slightly higher than that of 22%in Asia(22%). The genotype frequency of ALDH2*1/*1 in ALD group was significantly higher than that in HC group[93.7% (207/221)vs 69.0%(204/296),OR=6.668,p<0.0001]and the genotype frequency of allele ALDH 2*1 in ALD group was also significantly higher than that in HC group[96.8%(428/442)vs 82.9%(491/592),OR=6.289,p< 0.0001].ALD group had lower genotype frequency of ALDH2*1/*2,ALDH2*2/*2 and allele ALDH2*2 than those of HC group[6.3%(14/221)vs 28.0%(83/296),OR=0.174,p<0.0001;0%(0/221)vs 3.0%(9/296),OR=0.13,p< 0.05;3.2%(14/442)vs 17.1%（101/592),OR=0.159,p<0.01].There was no significant difference in distributivecharacteristics of gene polymorphism of ALDH2 at various stages of ALD development.Compared with those who carried ALDH2*1/*1,drinkers who carried ALDH2*2 were likely to develop ALD with less alcohol consumption（p<0.05).Conclusions Allele ALDH2*1 was one of the risk factors for the development of ALD in drinkers, but only in condition of heavy and long-term drinking.Allele ALDH2*2 could“protect”human from developing ALD,however,drinkers with allele ALDH 2*2 might develop ALD with less alcohol consumption and shorter drinking history.

【Key words】ALDH2;Gene polymorphism;Alcoholic liver disease;Drinking features

酒精性肝病（Alcoholic liver disease，ALD）是指长期大量饮酒导致的肝脏疾病[1,2]。ALD的发病率逐年升高。一项对2002年至2011年10年间中国“北方”地区住院肝硬化患者疾病谱特点及其变化趋势研究发现，酒精在病因上的构成比从3.3%上升至7.7%，住院的ALD患者占同期住院的肝病患者的比例也从2002年的1.74%上升至2011年的4.18%，10年间上升了2.4倍[3～5]。显然，酒精所致的肝脏损害已成为不容忽视的问题。摄入人体的酒精，除少部分可通过呼吸、汗液和尿液排出外，95%～98%则需要通过肝脏代谢。肝脏对酒精代谢主要由乙醇脱氢酶（Alcohol dehydrogenase，ADH）、乙醇氧化体系、微粒体乙醇氧化酶系统和过氧化氢酶系构成，共同负责将乙醇氧化为乙醛[6～9]。ADH系统负责70%酒精代谢，在还原型辅酶Ⅰ的参与下，ADH将乙醇代谢为乙醛，乙醛进而在乙醛脱氢酶（Acetaldehyde dehydrogenase 2，ALDH2）的作用下生成对人体无害的乙酸，后者进入三羧酸循环，最终代谢为水和二氧化碳，排出体外。……