Open Access Highly Accessed Research article

Functional polymorphism in aldehyde dehydrogenase-2 gene associated with risk of tuberculosis

Seung Kyu Park1, Choon-Sik Park2, Hyo-Suk Lee3, Kyong Soo Park4, Byung Lae Park5, Hyun Sub Cheong5 and Hyoung Doo Shin56*

Author Affiliations

1 Sorokdo National Hospital, 65 Doyang-eup, Goheung-gun, Jeonnam 548-904, Republic of Korea

2 Genome Research Center for Allergy and Respiratory Diseases, Soonchunhyang University Bucheon Hospital and Seoul Hospital, Seoul, Republic of Korea

3 Department of Internal Medicine and Liver Research Institute, Seoul National University, 28 Yungun-dong, Chongro-Gu, Seoul 110-744, Republic of Korea

4 Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-744, Republic of Korea

5 Department of Genetic Epidemiology, SNP Genetics, Inc., 1 Shinsu-dong, Mapo-gu, Seoul 121-742, Republic of Korea

6 Department of Life Science, Sogang University, 1 Shinsu-dong, Mapo-gu, Seoul 121-742, Republic of Korea

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BMC Medical Genetics 2014, 15:40  doi:10.1186/1471-2350-15-40

Published: 2 April 2014



The well-known genetic polymorphisms in ADH1B(His47Arg) and ALDH2(Glu487Lys) have dramatic effects on the rate of metabolizing alcohol and acetaldehyde. We investigated possible involvement of these functional polymorphisms in other common complex-trait diseases.


The genetic effects of these two polymorphisms on hepatitis, asthma, type-2 diabetes mellitus (T2DM), and tuberculosis (TB) were examined in a Korean population.


We demonstrated that the well-known functional polymorphism of a primary alcohol-metabolizing enzyme (ALDH2 Glu487Lys) has a strong genetic association with the risk of TB. The frequency of the minor allele (ALDH2*487Lys) was found to be much lower in TB patients (freq. = 0.099/n = 477) than among controls (freq. = 0.162/n = 796) (P = 0.00001, OR (95% confidential interval) = 0.57 (0.45-0.74)). Our data may indicate that TB was once an endemic disease, which exerted selection pressure for higher frequencies of ALDH2*487Lys in Asian populations. In addition, the calculated attributable fraction (AF) indicates that 39.5% of TB patients can attribute their disease to the detrimental effects of ALDH2Glu487Glu.


Our results suggest that this polymorphism is one of the genetic components of TB, at least in the Korean population.

Aldehyde dehydrogenase; Tuberculosis; Polymorphism