title: Polymorphism of Alcohol Metabolizing Gene ADH3 Predisposes to Development of Alcoholic Pancreatitis in North Indian Population.
abstract: OBJECTIVE
  Genetic factors regulating alcohol metabolism could predispose in developing alcoholic pancreatitis (ACP). Studies revealed that alcohol could be metabolized by both ways, oxidative and non-oxidative. The main oxidative pathway includes alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and cytochrome P450 enzyme. We investigated the association of polymorphisms in these enzymes with the alcoholic pancreatitis in the north Indian population.
  
  
  METHODS
  Patients with alcoholic pancreatitis (ACP; n = 72), tropical calcific pancreatitis (TCP; n = 75), alcoholic controls (AC; n = 40), and healthy controls (HC; n = 100) were included in the study. Blood samples were collected from the subjects in EDTA coated vials. DNA was extracted and genotyping for ADH3, ALDH2, and CYP2E1 was done by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism). The products were analyzed by gel electrophoresis.
  
  
  RESULTS
  The frequency distribution of ADH3(*)1/(*)1 genotype was significantly higher in ACP group (59.7%) compared with TCP (38.7%), HC (42%), and AC (37.5%) and was found to be associated with increased risk of alcoholic pancreatitis. There was no statistically significant difference between the frequency distribution of ADH3(*)1/(*)1, ADH3(*)1/(*)2, and ADH3(*)2/(*)2 genotypes between TCP and HC or healthy alcoholics. ALDH2 gene was monomorphic in our population, and the frequencies for CYP2E1 intron 6 Dra I polymorphism were comparable in all the four groups.
  
  
  CONCLUSIONS
  This study shows that carriers of ADH3(*)1/(*)1 individuals consuming alcohol are at higher risk for alcoholic pancreatitis than those with other genotypes such as ADH3(*)1/(*)2 and ADH3(*)2/(*)2.
authors.affiliation: Department of Biology, City College of New YorkNew York, NY, USA; Department of Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical SciencesLucknow, India.
authors.forename: Divya
authors.initials: D
authors.lastname: Singh
authors.affiliation: Department of Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences Lucknow, India.
authors.forename: Tajwar S
authors.initials: TS
authors.lastname: Negi
authors.affiliation: Department of Biology, City College of New York New York, NY, USA.
authors.forename: Ghanshyam
authors.initials: G
authors.lastname: Upadhyay
authors.affiliation: Department of Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical SciencesLucknow, India; Department of Gastroenterology and Hepatobiliary Sciences, Fortis Memorial Research InstituteGurgaon, India.
authors.forename: Gourdas
authors.initials: G
authors.lastname: Choudhuri
keywords: alcohol dehydrogenase; chronic pancreatitis; genetic polymorphism