Aims

To support the free and open dissemination of research findings and information on alcoholism and alcohol-related problems. To encourage open access to peer-reviewed articles free for all to view.

For full versions of posted research articles readers are encouraged to email requests for "electronic reprints" (text file, PDF files, FAX copies) to the corresponding or lead author, who is highlighted in the posting.

___________________________________________

Wednesday, November 23, 2011

Strong protective effect of the aldehyde dehydrogenase gene (ALDH2) 504lys (*2) allele against alcoholism and alcohol-induced medical diseases in Asia



Alcohol is oxidized to acetaldehyde, which in turn is oxidized to acetate. The aldehyde dehydrogenase 2 gene (ALDH2) is the most important gene responsible for acetaldehyde metabolism.

Individuals heterozygous or homozygous for the lys (A or *2) allele at the single nucleotide polymorphism (SNP) glu504lys (rs671) of
ALDH2 have greatly reduced ability to metabolize acetaldehyde, which greatly decreases their risk for alcohol dependence (AD).

Case–control studies have shown association between this SNP and alcohol dependence as well as alcohol-induced liver disease. However, some studies have produced insignificant results.

Using cumulative data from the past 20 years predominately from Asian populations (from both English and Chinese publications), this meta-analysis sought to examine and update whether the aggregate data provide new evidence of statistical significance for the proposed association.

Our results (9,678 cases and 7,331 controls from 53 studies) support a strong association of alcohol abuse and dependence, with allelic
P value of 3 × 10−56 and OR of 0.23 (0.2, 0.28) under the random effects model. The dominant model (lys–lys + lys–glu vs. glu–glu) also showed strong association with P value of 1 × 10−44 and OR of 0.22 (0.18, 0.27). When stricter criteria and various sub-group analyses were applied, the association remained strong (for example, OR = 0.23 (0.18, 0.3) and P = 2 × 10−28 for the alcoholic patients with alcoholic liver disease, cirrhosis, or pancreatitis).

These findings provide confirmation of the involvement of the human
ALDH2 gene in the pathogenesis of AD as well as alcohol-induced medical illnesses in East-Asians.



Read Full Article (PDF)