Investigation of alcohol metabolizing enzyme genes in chinese alcoholics with avascular necrosis of hip joint, pancreatitis and cirrhosis of the liver
Investigation of alcohol metabolizing enzyme genes in chinese alcoholics with avascular necrosis of hip joint, pancreatitis and cirrhosis of the liver
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DOI：
10.1093/alcalc/agg106
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发表时间：
2003-09-01
影响因子：
2.8
通讯作者：
Hsieh, TY
中科院分区：
文献类型：
--
作者：
Chao, YC;Wang, SJ;Hsieh, TY
目的和方法：酒精中毒可引起一系列疾病，包括髋关节缺血性坏死、肝硬化、胰腺炎和食管癌。诊断为AVN的中国酗酒患者肝硬化的发生率高于急性胰腺炎或食道癌。因此，本研究的目的是研究酒精代谢酶ADH2、ADH3、ALDH2和P4502E1在AVN（51例）、急性胰腺炎（92例）和肝硬化（159例）和280例非酒精患者亚群中多态性的遗传差异。结果：分析显示酒精性AVN患者ADH2*1等位基因频率明显低于肝硬化亚组。然而，酒精性AVN和胰腺炎亚组之间没有发现显著差异。此外，ALDH2*2的患病率在酒精亚组之间没有明显差异。与我们之前发表的食管癌酒精性患者的数据相比，本研究中酒精性AVN患者携带ADH2*1的频率明显降低。此外，酒精性AVN亚组的ALDH2*2携带频率明显低于食管癌患者。结论：ADH2*1和ALDH2*2的等位基因频率在存在特定酒精诱导疾病的酗酒亚群中存在差异，表明酒精代谢酶基因的遗传变异至少在一定程度上解释了所观察到的特定器官损伤类型。我们还发现AVN合并肝硬化比AVN合并急性胰腺炎更普遍。相比之下，AVN亚组的ADH2和ALDH2等位基因频率与急性胰腺炎亚组更相似，而与肝硬化亚组更相似。这些数据表明，其他遗传变异也可能影响中国酗酒者器官特异性并发症的类型。
Aims and Methods: Alcoholism may cause a range of diseases including avascular necrosis of the hip joint (AVN), cirrhosis of the liver, pancreatitis and oesophageal carcinoma. Chinese alcoholic patients diagnosed with AVN have a higher incidence of cirrhosis than of acute pancreatitis or oesophageal cancer. Thus, the aim of this study was to investigate genetic differences in polymorphisms of the alcohol-metabolizing enzymes ADH2, ADH3, ALDH2 and P4502E1 for subgroups of Chinese alcoholic patients, defined by diagnoses of AVN (n=51), acute pancreatitis (n=92) and liver cirrhosis (n=159), and for 280 non-alcoholic patients. Results: Analysis revealed that ADH2*1 allele frequency was significantly lower for the alcoholic AVN than for the cirrhosis subgroup. However, no significant difference was found between the alcoholic AVN and pancreatitis subgroups. Furthermore, ALDH2*2 prevalence was not found to differ significantly between the alcoholic subgroups. When compared with our previously published data for alcoholic patients with oesophageal carcinoma, ADH2*1 carriage was significantly less frequent for the alcoholic AVN patients in the current study. Further, ALDH2*2 carriage was significantly less frequent for the alcoholic AVN subgroup than for the oesophageal carcinoma patients. Conclusions: The allele frequencies for ADH2*1 and ALDH2*2 are different when comparing subpopulations of alcoholics defined by presence of specific alcohol-induced diseases, suggesting that genetic variation in alcohol-metabolizing enzyme genes accounts for, at least in part, the specific types of organ damage observed. We also found the combination of AVN and cirrhosis to be more prevalent than that of AVN and acute pancreatitis. In contrast, the ADH2 and ALDH2 allele frequencies for the AVN subgroup were more similar to those of the acute-pancreatitis than to the cirrhosis subgroup. These data indicate the possibility that other genetic variations may also influence the type of organ-specific complications in Chinese alcoholics.