Research Centre for Prevention and Health, The Capital Region of Denmark, Glostrup University Hospital, Glostrup, Denmark.
Clin Exp Allergy. 2010 Jan;40(1):123-30. doi: 10.1111/j.1365-2222.2009.03398.x.
Although 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.
To investigate the genetic determinants of self-reported alcohol-induced hypersensitivity reactions in Caucasians.
The 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.
In 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).
Our 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.
尽管在白种人中，饮酒后出现过敏反应很常见，但潜在机制和临床意义尚不清楚。相比之下，在亚洲人中，已经证实酒精性哮喘和潮红是由于单一核苷酸多态性（SNP），即乙醛脱氢酶 2（ALDH2）487lys 引起的，导致乙醛（乙醇的代谢产物）代谢减少和组胺水平升高。然而，这种 ALDH2 487lys 在白种人中不存在。
研究白种人自述的酒精引起的过敏反应的遗传决定因素。
该研究包括两项基于人群的研究，共纳入 1216 名和 6784 名居住在哥本哈根的成年人。通过问卷评估饮酒量和过敏反应（在亚组中进行），并将其与编码醇脱氢酶（ADHs）和 ALDHs 的基因的常见 SNP 相关联。
在两个群体中，具有快速代谢乙醇的遗传决定因素（ADH1b rs1229984 的 A 等位基因）的饮酒者发生酒精引起的过敏反应的风险增加（两个群体合并的 AA/AG 与 GG 比值：1.82，95%CI 1.04-3.17）。在两个群体中，发现一个编码 ALDH1b1 的常见 SNP（rs2228093）与酒精引起的过敏反应显著相关（两个群体合并的 TT 与 CC 比值：2.53，95%CI 1.31-4.90）。
我们的数据支持白种人酒精敏感性是由遗传决定的，并表明乙醛的组胺释放作用代表了一种合理的生物学机制。此外，我们首次报道了在白种人群中，乙醛代谢系统中具有临床意义的 SNP。
