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.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.

Airway Epithelium Plays a Leading Role in the Complex Framework Underlying Respiratory Allergy

“…Polymorphisms in IL-6 [68], IL-4 [69], high-affinity IgE receptor [70], IL-4R [71], disintegrin and metalloproteinase 33 [72], and IL-13 [73] have been associated with epithelial dismantling and malfunctioning, especially in the context of asthma and chronic obstructive pulmonary disease [74,75]. In this sense, a high level of IL-13 in asthmatic patients has been involved in wall remodeling processes [76,77].…”

Significant Association of Adam 33 Polymorphism with COPD in Javanese Population of Indonesia

“…Nevertheless, COPD genetic profiling use in the clinic is current limited to find out Alpha-1 antitrypsin deficiency (7,8) . Furthermore, the relationship between A disintegrin and metalloprotease 33 (ADAM33) polymorphisms and COPD has been reported by other researchers (9)(10)(11) .…”

“…In the Kashmiri population of India, ADAM33 gene polymorphism in three SNPs (T1, T2, and Q-1) were obviously associated with COPD (11) . The results of present study showed that the similarities of findings in T1 and T2, but Q-1 was different.…”

“…Moreover, the reported research was strengthened by several similar studies in European and Asian regions such as India, China and Mongolia. Polymorphisms in ADAM33 to airway hyper-responsiveness have been correlated to airway inflammation in COPD, and accelerated lung function decline by other research (11,13,15) . As association between low lung function and high mortality risk, particularly on account of COPD, it is important to explore the genetic components that escalate susceptibility to lung function decrease and COPD.…”