title: A disintegrin and metalloprotease 33 polymorphism association with COPD in long-term tobacco smokers of the ethnic Kashmiri population of India.
abstract: BACKGROUND
  Chronic obstructive pulmonary disease (COPD) is characterized by an interaction of various environmental influences especially cigarette smoking and genetic determinants. The prevalence of this disease is ever increasing and characterization of the genetic determinants of the disease has been undertaken globally. The 'A disintegrin and metalloprotease 33' (ADAM 33) gene is one candidate gene that has been studied.
  
  
  OBJECTIVE
  Our objective was to investigate whether single nucleotide polymorphisms in ADAM33 gene are associated with COPD in long-term tobacco smokers in the ethnic Kashmiri population of northern India.
  
  
  METHODS
  This was a randomized case-control study, which included 78 stable COPD (GOLD stage11-IV) patients, who were compared with 77 age- and sex-matched long-term tobacco smokers (>20 pack years) without any evidence of COPD. Polymorphic analysis for three single nucleotide polymorphisms (SNPs), (T1, T2, and Q1) of the ADAM33 gene was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) followed by sequencing. The data were analyzed by descriptive statistics and comparative evaluation was done by parametric/non-parametric tests.
  
  
  RESULTS
  The analysis of the T1, T2, and Q1 SNPs, revealed that the frequencies of the T2GG, T1GG, and the Q1AG genotypes were significantly higher in patients with COPD in comparison with the controls (P < 0.001). Similarly, the T1G and T2G allele frequency was higher in the patients than in the controls (p = 0.177 and 0.43, respectively).
  
  
  CONCLUSIONS
  Three SNPs of the ADAM33 gene were significantly associated with COPD in the Kashmiri population of India. This study establishes the possible role of ADAM33 SNPS in the causation of COPD. Further studies across different geographical areas in the country will unravel the contribution of this gene in the causation of COPD in India.
authors.affiliation: Department of Internal and Pulmonary Medicine, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India.
authors.forename: Sonaullah
authors.initials: S
authors.lastname: Shah
authors.affiliation: Department of Internal and Pulmonary Medicine, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India.
authors.forename: Amir
authors.initials: A
authors.lastname: Rashid
authors.affiliation: Department of Immunology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India.
authors.forename: Zaffar A
authors.initials: ZA
authors.lastname: Shah
authors.affiliation: Department of Internal and Pulmonary Medicine, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India.
authors.forename: Rafi Ahmad
authors.initials: RA
authors.lastname: Jan
authors.affiliation: Department of Internal and Pulmonary Medicine, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India.
authors.forename: Umar Hafiz
authors.initials: UH
authors.lastname: Khan
authors.affiliation: Department of Immunology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India.
authors.forename: Imtiyaz A
authors.initials: IA
authors.lastname: Bhat
authors.affiliation: Department of Internal and Pulmonary Medicine, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India.
authors.forename: Suhail
authors.initials: S
authors.lastname: Mantoo
authors.affiliation: Department of Internal and Pulmonary Medicine, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India.
authors.forename: Tajamul H
authors.initials: TH
authors.lastname: Shah
authors.affiliation: Department of Internal and Pulmonary Medicine, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India.
authors.forename: Parvaiz A
authors.initials: PA
authors.lastname: Koul
keywords: A disintegrin and metalloprotease 33 polymorphism; chronic obstructive pulmonary disease; smoking