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. 2015 May-Jun;32(3):220-4.
doi: 10.4103/0970-2113.156222.

A disintegrin and metalloprotease 33 polymorphism association with COPD in long-term tobacco smokers of the ethnic Kashmiri population of India

Sonaullah Shah  1 , Amir Rashid  1 , Zaffar A Shah  2 , Rafi Ahmad Jan  1 , Umar Hafiz Khan  1 , Imtiyaz A Bhat  2 , Suhail Mantoo  1 , Tajamul H Shah  1 , Parvaiz A Koul  1
Affiliations

A disintegrin and metalloprotease 33 polymorphism association with COPD in long-term tobacco smokers of the ethnic Kashmiri population of India

Sonaullah Shah et al. Lung India. 2015 May-Jun.

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.

Materials and 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).

Conclusion: 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.

Keywords: A disintegrin and metalloprotease 33 polymorphism; chronic obstructive pulmonary disease; smoking.

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Conflict of interest statement

Conflict of Interest: None of the authors have any declaration of interest to disclose. All the authors have equally contributed in writing up of this manuscript.

Figures

Figure 1
Figure 1
RFLP picture of ADAM 33 T1 SNP A/G after restriction digestion with NcoI (3%) agarose gel electrophoresis. Lane 1-100 bp DNA Marker. Lane 2-Blank. Lanes 5, 9 heterozygous AG (400 and 260 bp, 140 bp), Lanes 3, 4, 6, 7, 8 homozygous wild AA (260 bp, 140 bp), Lanes 10 homozygous GG
Figure 2
Figure 2
RFLP picture of ADAM 33 T2 SNP A/G after restriction digestion with HpyCH4III (3%) agarose gel electrophoresis. Lane 1: 100 bp DNA Marker. Lanes 6, 7 homozygous GG (312 bp). Lanes 2, 4, 5, 8, 9 heterozygous AG (310 and 198 bp, 112 bp), Lanes 3 homozygous AA (198 bp, 112 bp)
Figure 3
Figure 3
RFLP picture of ADAM 33 Q-1 SNP A/G after restriction digestion with BtsCI (20% PAGE) agarose gel electrophoresis. Lane 6: 50 bp DNA Marker. Lanes 3, 5, 7 heterozygous AG (158 and 138 bp, 20 bp), Lane 4 homozygous AA (138 bp, 20 bp), Lanes 1, 2, 8 homozygous GG (158 bp)
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