title: Functional polymorphism in aldehyde dehydrogenase-2 gene associated with risk of tuberculosis.
abstract: BACKGROUND
  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.
  
  
  METHODS
  The genetic effects of these two polymorphisms on hepatitis, asthma, type-2 diabetes mellitus (T2DM), and tuberculosis (TB) were examined in a Korean population.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Our results suggest that this polymorphism is one of the genetic components of TB, at least in the Korean population.
authors.forename: Seung Kyu
authors.initials: SK
authors.lastname: Park
authors.forename: Choon-Sik
authors.initials: CS
authors.lastname: Park
authors.forename: Hyo-Suk
authors.initials: HS
authors.lastname: Lee
authors.forename: Kyong Soo
authors.initials: KS
authors.lastname: Park
authors.forename: Byung Lae
authors.initials: BL
authors.lastname: Park
authors.forename: Hyun Sub
authors.initials: HS
authors.lastname: Cheong
authors.affiliation: Department of Genetic Epidemiology, SNP Genetics, Inc,, 1 Shinsu-dong, Mapo-gu, Seoul 121-742, Republic of Korea. hdshin@sogang.ac.kr.
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D019943:Amino Acid Substitution; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D056910:Republic of Korea; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D014397:Tuberculosis, Pulmonary / Q000201:enzymology / Q000235:genetics*; D055815:Young Adult
chemical_list: C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial