Genetic determinants of both ethanol and acetaldehyde metabolism influence alcohol hypersensitivity and drinking behaviour among Scandinavians
Genetic determinants of both ethanol and acetaldehyde metabolism influence alcohol hypersensitivity and drinking behaviour among Scandinavians
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DOI：
10.1111/j.1365-2222.2009.03398.x
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发表时间：
2010-01-01
影响因子：
6.1
通讯作者：
Husemoen, L. L. N.
中科院分区：
文献类型：
--
作者：
Linneberg, A.;Gonzalez-Quintela, A.;Husemoen, L. L. N.
尽管摄入酒精饮料后的过敏反应在白种人中很常见，但其潜在机制和临床意义尚不清楚。相比之下，在亚洲人中，酒精引起的哮喘和潮红已被证明是由于单核苷酸多态性 (SNP)，即乙醛脱氢酶 2 (ALDH2) 487lys，导致乙醛（乙醇的代谢产物）代谢减少和组胺水平升高。然而，白种人中不存在 ALDH2 487lys。目的调查白种人自我报告的酒精诱发超敏反应的遗传决定因素。方法该研究包括两项基于人群的研究，对象为居住在哥本哈根的 1216 名和 6784 名成年人。酒精消耗和超敏反应（亚组）的评估通过问卷进行，并与编码乙醇脱氢酶（ADH）和 ALDH 的基因的常见 SNP 相关。结果在两个人群中，具有基因决定的乙醇快速代谢（ADH1b rs1229984 的 A 等位基因）的饮酒者发生酒精诱发超敏反应的风险增加（比值比 AA/AG 与 GG 结合）人群：1.82，95% CI 1.04-3.17）。在这两个人群中，发现编码 ALDH1b1 (rs2228093) 的常见 SNP 与酒精引起的超敏反应显着相关（联合人群中 TT 与 CC 的比值比：2.53，95% CI 1.31-4.90）。结论我们的数据支持白种人的酒精敏感性是由基因决定的，并表明乙醛的组胺释放作用代表了一种合理的可能性。生物学机制。此外，我们首次报告了白种人乙醛代谢系统中具有临床意义的 SNP。引用如下：A. Linneberg、A. Gonzalez-Quintela、C. Vidal、T. J 圆分割 rgensen、M. Fenger、T. Hansen、O. Pedersen 和 L. L. N. Husemoen，临床与实验过敏，2010 (40) 123-130。
P>BackgroundAlthough hypersensitivity reactions following intake of alcoholic drinks are common in Caucasians, the underlying mechanisms and clinical significance are not known. In contrast, in Asians, alcohol-induced asthma and flushing have been shown to be because of a single nucleotide polymorphism (SNP), the acetaldehyde dehydrogenase 2 (ALDH2) 487lys, causing decreased acetaldehyde (the metabolite of ethanol) metabolism and high levels of histamine. However, the ALDH2 487lys is absent in Caucasians.ObjectivesTo investigate the genetic determinants of self-reported alcohol-induced hypersensitivity reactions in Caucasians.MethodsThe study included two population-based studies of 1216 and 6784 adults living in Copenhagen. Assessment of alcohol consumption and hypersensitivity reactions (in a subgroup) was performed by a questionnaire and was related to common SNPs of genes encoding alcohol dehydrogenases (ADHs) and ALDHs.ResultsIn both populations, alcohol drinkers with a genetically determined fast metabolism of ethanol (the A allele of the ADH1b rs1229984) had an increased risk of alcohol-induced hypersensitivity reactions (odds ratio AA/AG vs. GG in combined populations: 1.82, 95% CI 1.04-3.17). In both populations, a common SNP encoding ALDH1b1 (rs2228093) was found to be significantly associated with alcohol-induced hypersensitivity (odds ratio TT vs. CC in combined populations: 2.53, 95% CI 1.31-4.90).ConclusionsOur data support that alcohol sensitivity in Caucasians is genetically determined and suggest that a histamine-releasing effect of acetaldehyde represents a plausible biological mechanism. Furthermore, we present the first report of a clinically significant SNP within the acetaldehyde-metabolizing system in a Caucasian population.Cite this as: A. Linneberg, A. Gonzalez-Quintela, C. Vidal, T. J circle divide rgensen, M. Fenger, T. Hansen, O. Pedersen and L. L. N. Husemoen, Clinical & Experimental Allergy, 2010 (40) 123-130.