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

The correlation between gene polymorphism of acetaldehyde dehydrogenase 2 and drinking features as well as disease onset in patients with alcoholic liver disease

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Taq Man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%);ALDH2*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];ALDH2*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。

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 ALDH2 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 ALDH2＊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 distributive characteristics 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＊I 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 ALDH2＊2 might develop ALD with less alcohol consumption and shorter drinking history.