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The IUP Journal of Genetics & Evolution
Association of ADAM33 Gene Polymorphisms with Reduction of Lung Function as Measured by Peak Expiratory Flow Rate Among Healthy Male Smokers and Nonsmokers
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ADAM33 gene, which comes in ADAM (a disintegrin and metalloprotease) gene family, is an asthma susceptibility gene and has been associated with impaired lung function. Therefore, we aimed to investigate association of five ADAM33 polymorphisms (F+1 (rs511898) G/A, S2 (rs528557) G/C, ST+4 (rs44707) A/C, ST+5 (rs597980) C/T and V4 (rs2787094) C/G) with lung function, as assessed by peak expiratory flow (PEF) meter in normal healthy male population recruited from among students and employee volunteers in the age group of 16 to 50 year, including smokers and nonsmokers. SNPs were genotyped with the help of restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) method. Of 201 healthy males recruited, 50 (24.9%) were smokers and 151 (75.1%) were nonsmokers. Smokers had statistically significant lower values of PEFR as compared to nonsmokers. With lowest values in those smoking > 10 cigarettes/day compared to those smoking 1-2 and 2-10 cigarettes/day (p < 0.001 and < 0.035, respectively). Only among smokers, mean difference of PEFR was statistically significantly lower in heterozygous genotypes when compared to mutants of SNP V4 (p = 0.033). This may possibly be explained on the basis of gene-environmental interaction and further research is needed in this area.

 
 
 

Smoking is a well-established major risk factor for chronic obstructive pulmonary disease (COPD) and impedes with response to treatment in patients with asthma and COPD (Hylkema et al., 2007). Cigarette smoking can be considered as a major global health hazard. It has been estimated that about 450 million adults would be killed by smoking between 2000 and 2050 (Prabhat Jha, 2009). Many epidemiological and family studies have pointed out that genes that predispose to asthma interact with environmental tobacco smoke exposure in early life (Xu and Weiss, 2002; Choudhry et al., 2005; and Meyers et al., 2005). A gene encoding a disintegrin and metalloprotease (ADAM33) located on chromosome 20p13 was first identified as an asthma susceptibility gene by positional cloning approach in the year 2002 in a genome-wide scan of a Caucasian population (Van Eerdewegh et al., 2002). This gene was found to be associated with COPD and lung function in long-term tobacco smokers (Sadeghnejad et al., 2009). A published study has also showed that association of ADAM33 polymorphisms with lung function decline in the general population among tobacco smokers (Van Diemen et al., 2005). Therefore, we aimed at investigating association of five single nucleotide polymorphisms (SNP) of ADAM33 (F+1 (rs511898) G/A, S2 (rs528557) G/C, ST+4 (rs44707) A/C, ST+5 (rs597980) C/T and V4 (rs2787094) C/G) with lung function, as calculated by peak expiratory flow (PEF) meter in normal healthy male population, including smokers and nonsmokers.

This study was conducted in Chhattrapati Shahuji Maharaj Medical University, Lucknow, India, and was part of a larger study "to assess the role of ADAM33 Gene expression in diagnosis and management of asthmatics." We included healthy males between 16 years and 50 years of age group who were either medical resident doctors or employees of the hospital. Included were those who fulfilled inclusion criteria and gave consent of participation. The criteria for selecting subjects were: (a) No past or present physician's diagnosis of asthma and other pulmonary and heart diseases; (b) No history of wheezing, shortness of breath, and other symptoms of heart and lung diseases; (c) No use of medications for pulmonary and heart disease; and (d) Absence of first-degree relatives with a history of asthma. Prior to inclusion, subjects were examined carefully to rule out any underlying heart, lung or general disease. All subjects were personally interviewed about their age, medical history of other diseases, demographic features, family history of asthma/other pulmonary disease, present smoking habit and number of bidi/cigarette consumption per day, residence near heavy traffic and presence of smoke emitting industry near residence.

 
 
 

Genetics & Evolution Journal, ADAM33 Gene Polymorphisms, Healthy Male Smokers and Nonsmokers, Chronic Obstructive Pulmonary disease, Heterozygous Genotypes, Cigarette Smoking, Smoke Emitting Industries, Homozygous Mutant Genotype, Heterozygous Genotype, Epidemiological Studies.