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中国髋关节缺血性坏死、胰腺炎及肝硬化酒精性患者酒精代谢酶基因的研究

Investigation of alcohol metabolizing enzyme genes in Chinese alcoholics with avascular necrosis of hip joint, pancreatitis and cirrhosis of the liver.

作者信息

Chao You-Chen, Wang Shyu-Jye, Chu Heng-Cheng, Chang Wei-Kuo, Hsieh Tsai-Yuan

机构信息

Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325 Section 2 Cheng-Kung Road, Neihu, Taipei, Taiwan, Republic of China.

出版信息

Alcohol Alcohol. 2003 Sep-Oct;38(5):431-6. doi: 10.1093/alcalc/agg106.

Abstract

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 ADH21 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, ALDH22 prevalence was not found to differ significantly between the alcoholic subgroups. When compared with our previously published data for alcoholic patients with oesophageal carcinoma, ADH21 carriage was significantly less frequent for the alcoholic AVN patients in the current study. Further, ALDH22 carriage was significantly less frequent for the alcoholic AVN subgroup than for the oesophageal carcinoma patients.

CONCLUSIONS

The allele frequencies for ADH21 and ALDH22 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.

摘要

目的与方法

酗酒可能引发一系列疾病,包括髋关节缺血性坏死(AVN)、肝硬化、胰腺炎和食管癌。被诊断患有AVN的中国酗酒患者中,肝硬化的发病率高于急性胰腺炎或食管癌。因此,本研究的目的是调查酒精代谢酶ADH2、ADH3、ALDH2和P4502E1基因多态性在中国酗酒患者亚组中的遗传差异,这些亚组根据诊断分为AVN组(n = 51)、急性胰腺炎组(n = 92)和肝硬化组(n = 159),并与280名非酗酒患者进行比较。

结果

分析显示,酒精性AVN患者的ADH21等位基因频率显著低于肝硬化亚组。然而,酒精性AVN组与胰腺炎亚组之间未发现显著差异。此外,酒精性亚组之间的ALDH22患病率未发现显著差异。与我们之前发表的酒精性食管癌患者数据相比,本研究中酒精性AVN患者携带ADH21的频率显著更低。此外,酒精性AVN亚组携带ALDH22的频率显著低于食管癌患者。

结论

在比较由特定酒精诱导疾病定义的酗酒亚人群时,ADH21和ALDH22的等位基因频率不同,这表明酒精代谢酶基因的遗传变异至少部分解释了所观察到的特定类型的器官损伤。我们还发现AVN与肝硬化的组合比AVN与急性胰腺炎的组合更常见。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,而与肝硬化亚组不同。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类型的可能性。

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