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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 analyze the relationship between alcohol dehydrogenase 2 (ALDH2) gene polymorphism and alcohol consumption in patients with alcoholic liver disease (ALD). Methods TaqMan real-time PCR was used to detect polymorphisms of ALDH2 gene in 296 unrelated healthy controls (HCs) and 221 patients with ALD. The association between ALDH2 gene polymorphism and alcohol consumption and disease status were analyzed. Results The frequency of ALDH2 mutation was 31.1% (92/296) in healthy subjects, which was much higher than that in other countries (almost zero) in Europe, America and Africa, slightly higher than the average level in Asia (22%). The ALDH2 * 1 / * 1 genotype The frequency of ALDH2 * 1 allele in patients with ALD was significantly higher than that in healthy subjects [93.7% (207/221) vs 69.0% (204/296), OR = 6.668, P <0.0001] The frequency of ALDH2 * 1 / * 2 genotype was significantly lower in ALD patients than that in healthy subjects [96.8% (428/442) vs 82.9% (491/592), OR = 6.289, P <0.0001] The frequency of ALDH2 * 2 / * 2 genotype was also significantly lower in patients with ALD than that in healthy subjects [0% (0/221),% (14/221) Vs 28.0% (83/296), OR = 0.174, P <0.0001] ) Vs 3.0% (9/296), OR = 0.13, P <0.05]. The ALDH2 * 2 allele frequency was also significantly lower in ALD patients than that in healthy controls [3.2% (14/442) vs 17.1% (101/592), OR = 0.159, P <0.01] There was no statistically significant difference in the distribution of disease progression between patients with ALDH2 * 1 / * 1 genotypes and those with ALDH2 * 2 genotypes who developed ALDH2 * 1 / * 1 genotype at lower total alcohol consumption All <0.05). Conclusions ALDH2 * 1 allele is an important risk factor of ALD in drinkers. ALDH2 * 1 allele can occur ALDH2 * 2 allele when drinking more alcohol and longer time. ALDH2 * 2 allele can prevent ALD , But drinkers develop ALD with less alcohol and less alcohol.