Genetic polymorphism of GSTT1 and GSTM1 and susceptibility to chronic obstructive pulmonary disease (COPD)
Introduction
Chronic obstructive pulmonary disease (COPD) represents a major public health care problem worldwide due to its increasing prevalence, morbidity, and mortality [1]. Although COPD is now the 12th largest burden in the world, it is estimated that it will rise to be the fifth largest burden by 2020 [2]. Chronic obstructive pulmonary disease is known to be the fourth leading cause of death and the only cause of death, which is increasing [3]. Chronic obstructive pulmonary disease is characterized by airflow limitation that is not fully reversible, which usually progresses, together with an abnormal inflammatory response to noxious particles or gases. Patients may have chronic bronchitis, emphysema, small airways diseases, or a combination of these, with or without systemic manifestations of the disease [4].
It is generally accepted that cigarette smoking is the most important risk factor for COPD. Nevertheless, only 10% to 20% of chronic smokers develop the severe impairment of pulmonary functions associated with COPD. This indicates the possible contribution of environmental cofactors to the development of COPD [5]. Another possible reason why only a small proportion of smokers develop COPD might be genetic variation in the enzymes that detoxify cigarette smoke products. These enzymes include mEPHX, GST, and CYP1A1, and this indicates the presence of genetic predisposing factors in its pathogenesis [3]. GSTs are a super family of enzymes involved in the conjugation of a wide range of electrophilic substances with glutathione, thereby, facilitating detoxification and further metabolism and excretion. Among the isoenzymes of GST, the homozygous GSTM1-null genotype has been reported to show some association with the pathogenesis of lung cancer and, especially, emphysema [5].
GSTT1 conjugates glutathione and various potential carcinogens, which are present in cigarette smoke, and its null type mutant has been suggested as a risk factor for many diseases. There is increasing evidence that several genes influence the development of COPD [3].
To test the hypothesis that genetic polymorphism of GSTT1 and/or GSTM1 is associated with COPD in smokers.
Section snippets
Materials and methods
The study group consisted of 34 patients with 10 or more years of smoking-related COPD recruited from Ain Shams Hospital, Cairo, Egypt. Chronic obstructive pulmonary disease was diagnosed on the basis of medical history, chest radiographic findings, physical examination, and spirometric data, according to American Thoracic Society guidelines [6]. The control group included 34 asymptomatic smokers or ex-smokers with smoking history of 10 or more pack-years without clinical or laboratory evidence
Results
The frequency of carriers of null GSTT1 genotype was 50% among cases in the COPD group compared to 44.1% in the control group. Carriers of null GSTT1 were at minor risk of developing COPD when compared with carriers of the wild GSTT1 genotype (OR, 1.3; 95% CI, 0.5-3.2). In case of GSTM1, the frequency of carriers of null GSTM1 genotype was 52.9% among cases compared to 26.5% in controls. Carriers of null GSTM1 were at much higher risk of developing COPD (OR, 3.1; 95% CI, 1.1-8.6). Furthermore,
Discussion
Chronic obstructive pulmonary disease is a complex multifactorial disease, and it has been suggested that a complicated interplay between environmental and genetic factors is likely to be involved in its development[12], [13], [14]. Cigarette smoking has been generally accepted as one of the most important environmental factors[12], [13], [15]. However, only a relatively small proportion of heavy smokers develop COPD, which indicates that there is genetic basis for COPD. Detoxification genes
Conclusion
Our data provide evidence that smokers with null genotype of GSTM1 were more susceptible for developing COPD. Furthermore, they are usually more susceptible for rapid decline in lung function. Novel genes would allow the assessment of new mechanisms and pathways in disease and provide new therapeutic opportunities. At-risk individuals could be identified by screening and strongly advised to abstain from smoking and avoid occupations where there are high loads of environmental dusts.
Acknowledgments
This study was done under kind supervision of Dr Neveen Salah El Din (biochemistry department) and Dr Marwa (community medicine department). Thanks to Dr Sahar Elhannan and Mr Khan for their technical support.
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