Pastorelli R, Bardazzi G, Saieva C, Cerri A, Gestri D, Allamani A, Airoldi L, Palli D
Molecular Toxicology Laboratory, Istituto di Richerche Farmacologiche Mario Negri, Milan, Italy.
Alcohol Clin Exp Res. 2001 Feb;25(2):221-7.
Although multiple genes are involved in alcoholism and can contribute differently to the risk of dependence and liver damage, no studies have investigated susceptibility to addiction in combination with susceptibility to liver damage due to differences in ethanol metabolism.
We evaluated the role of three polymorphic genes related to alcohol metabolism (CYP2E1) and, possibly, dependence (DRD2 and SLC6A4 promoter) in a series of 60 alcoholics admitted to a specialized referral center in Florence, Italy. Eighteen had a diagnosis of liver cirrhosis. A control series of 64 blood donors were identified at the same hospital. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism methods.
No difference was found in the frequency of the CYP2E1 Rsal c2 allele (2.5% among alcoholics and 4.7% among controls) and the DraI C allele (6.7% and 10.1%). Similarly, no difference was found in the frequency of the DRD2 A1 allele (15.8% and 13.3%) and the B1 allele (10.8% and 8.6%). The proportion of controls with a combined B1 genotype (B1/B1 or B1/B2) was significantly associated with smoking (p = 0.03). The distribution of the S and L allele of the SLC6A4 gene was similar in the two groups, with 15% and 14%, respectively, homozygous S/S carriers. A significant association, however, emerged in the group of alcoholics, with a five times higher risk for S/S carriers of developing cirrhosis (p < 0.05). This association with liver persisted even after exclusion of the subgrouped of 10 hepatitis C virus positive alcoholics.
Overall, our results provided no evidence of an increased susceptibility to develop alcoholism that was associated with the three genotypes investigated, either alone or in combination. An increased risk of developing liver cirrhosis for S/S homozygous carriers among alcohol-dependent patients was observed for the first time.
尽管多种基因与酒精中毒有关，且对依赖风险和肝损伤的影响各不相同，但尚无研究因乙醇代谢差异而综合研究成瘾易感性与肝损伤易感性。
我们评估了与酒精代谢相关的三个多态性基因（CYP2E1）以及可能与依赖相关的基因（DRD2和SLC6A4启动子）在意大利佛罗伦萨一家专门转诊中心收治的60名酗酒者中的作用。其中18人被诊断为肝硬化。在同一家医院确定了64名献血者作为对照系列。通过聚合酶链反应-限制性片段长度多态性方法进行基因分型。
未发现CYP2E1 Rsal c2等位基因（酗酒者中为2.5%，对照组中为4.7%）和DraI C等位基因（分别为6.7%和10.1%）的频率存在差异。同样，DRD2 A1等位基因（分别为15.8%和13.3%）和B1等位基因（分别为10.8%和8.6%）的频率也未发现差异。具有联合B1基因型（B1/B1或B1/B2）的对照组比例与吸烟显著相关（p = 0.03）。SLC6A4基因的S和L等位基因在两组中的分布相似，纯合S/S携带者分别为15%和14%。然而，在酗酒者组中出现了显著关联，S/S携带者患肝硬化的风险高出五倍（p < 0.05）。即使排除了10名丙型肝炎病毒阳性酗酒者亚组后，这种与肝脏的关联仍然存在。
总体而言，我们的结果没有提供证据表明单独或联合研究的三种基因型与酒精中毒易感性增加有关。首次观察到酒精依赖患者中S/S纯合携带者患肝硬化的风险增加。
