Chao Y C, Young T H, Tang H S, Hsu C T
Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Hepatology. 1997 Jan;25(1):112-7. doi: 10.1002/hep.510250121.
It is still not clear why some alcoholic patients acquire certain organ-specific complications of alcoholism whereas other alcoholic patients acquire different ones. As we know the liver alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and cytochrome P4502E1 (P4502E1) are polymorphic at the ADH2, ADH3, and ALDH2 loci and the 5'-flanking region of the P4502E1. The aim of this study was to investigate the differences between Chinese alcoholic patients with cirrhosis and acute pancreatitis by studying the genetic polymorphisms of ADH2, ADH3, ALDH2, and P4502E1. Genotyping of ADH2, ADH3, ALDH2, and P4502E1 was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods on peripheral white blood cell DNA from 75 alcoholic cirrhotic patients, 48 acute alcoholic pancreatitis patients, 19 heavy drinkers without liver disease or pancreatitis, and 235 controls. The results showed that the frequencies of the alleles ADH21 and ALDH21 in the alcoholic cirrhotic patients were significantly higher than those in the nonalcoholic controls. In acute alcoholic pancreatitis patients, only the frequency of allele ALDH21, not ADH21 was significantly higher than in the nonalcoholic controls. The allele frequency of ADH21 in acute pancreatitis patients was significantly lower (P < .01) than in alcoholic cirrhotic patients. The daily amount of alcohol consumption was significantly lower in patients with acute pancreatitis than in patients with cirrhosis (P < .0005). The genotype distributions of P4502E1, detected by RsaI and PstI, were not different among alcoholic cirrhotic patients, alcoholic pancreatitis patients, heavy drinker, and nonalcoholic controls. In conclusion, ALDH21 is the most important alcohol metabolizing gene affecting predisposition to alcoholism whereas the ADH2*2 gene may influence susceptibility to acute alcoholic pancreatitis. The patients with alcohol-induced cirrhosis and with alcohol-induced acute pancreatitis are of two different subpopulations.
目前仍不清楚为什么一些酗酒患者会出现酒精中毒的某些器官特异性并发症，而其他酗酒患者却出现不同的并发症。我们知道肝脏中的乙醇脱氢酶（ADH）、乙醛脱氢酶（ALDH）和细胞色素P4502E1（P4502E1）在ADH2、ADH3和ALDH2基因座以及P4502E1的5'侧翼区域具有多态性。本研究的目的是通过研究ADH2、ADH3、ALDH2和P4502E1的基因多态性，探讨中国酗酒性肝硬化患者和急性胰腺炎患者之间的差异。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法，对75例酒精性肝硬化患者、48例急性酒精性胰腺炎患者、19例无肝脏疾病或胰腺炎的重度饮酒者以及235例对照者的外周血白细胞DNA进行ADH2、ADH3、ALDH2和P4502E1基因分型。结果显示，酒精性肝硬化患者中ADH21和ALDH21等位基因频率显著高于非酒精性对照者。在急性酒精性胰腺炎患者中，只有ALDH21等位基因频率显著高于非酒精性对照者，而ADH21则不然。急性胰腺炎患者中ADH21等位基因频率显著低于酒精性肝硬化患者（P <.01）。急性胰腺炎患者的每日酒精摄入量显著低于肝硬化患者（P <.0005）。通过RsaI和PstI检测的P4502E1基因型分布在酒精性肝硬化患者、酒精性胰腺炎患者、重度饮酒者和非酒精性对照者之间没有差异。总之，ALDH21是影响酒精中毒易感性的最重要酒精代谢基因，而ADH2*2基因可能影响对急性酒精性胰腺炎的易感性。酒精性肝硬化患者和酒精性急性胰腺炎患者属于两个不同的亚群。
