Genetic and environmental modulation of chronic obstructive pulmonary disease
Introduction
Both genetic (Silverman et al., 1998, Barnes, 1999) and environmental (Kauffman et al., 1982, Love and Miller, 1982, Sparrow et al., 1982, Wegman et al., 1982, Becklake, 1985, Korn et al., 1987, Becklake, 1989, Cowie and Mabena, 1991, Xu et al., 1992, Christiani et al., 1994) factors affect an individual's risk for chronic obstructive pulmonary disease (COPD), a disorder that broadly includes the range of pulmonary pathology from bronchial inflammation to emphysema (ATS, 1995). Less well studied is the manner in which environmental factors interact with genetic factors in contributing to COPD risk. This is partially due to the pitfalls and limitations of current methodological approaches to dissecting the gene and environment contributions to any complex disease in which multiple genes and multiple exposures may alter the phenotypic expression of the disorder. What follows is a discussion of: (1) evidence for genetic susceptibility for COPD; (2) evidence of environmental risk for COPD; (3) evidence for a genetic and environmental interaction for the risk of COPD based on our recent studies of the best understood form of genetic susceptibility to COPD: severe alpha1-antitrypsin (α1AT) deficiency.
Section snippets
Genetic risk for COPD
Epidemiologic studies have demonstrated aggregation of COPD among relatives, but without clear Mendelian inheritance. Household aggregations of chronic bronchitis were found in a randomly selected group in Massachusetts (Tager et al., 1976). In addition, FEV1 was significantly correlated between siblings and between female children and their parents, but less clearly between spouses. Using case-control methodology, researchers have shown that chronic bronchitis and lower FEV1 were more
Environmental Risk for COPD
Tobacco smoking is recognized as the single most important risk factor for development of COPD (ATS, 1995). This review will not focus on the ample evidence linking personal tobacco smoke with COPD, but will focus on other important contributing environmental factors including dust, fumes, and environmental tobacco smoke (ETS).
The role of occupational and environmental exposures in airway disease was supported in three large well-designed community studies. Specifically, the Harvard six cities
Genetic and environment interactions in α1AT deficiency
The case of α1AT deficiency is illustrative and serves as a model disorder in which to investigate effects of environmental factors in a genetically susceptible patient population. Tobacco smoking is the principal environmental risk factor associated with the development of chronic airflow obstruction individuals with severe α1AT deficiency, phenotype PI*Z (Larsson, 1978, Tobin et al., 1983, Janoff, 1985, Silverman et al., 1989). The mean age of onset of symptoms is 30–40 years of age in
Implications for future studies
COPD is the consequence of an overriding effect of environmental exposures on the lung. Several decades of research have successfully identified a number of those exposures, especially tobacco smoke. It appears that the extent of the lung damage caused by those insults may be modulated by genetic or other host factors. Further identification of genetic factors predisposing certain individuals to increased COPD risk is an important goal of the ongoing research using DNA microarrays, differential
References (84)
Influence of passive smoking and parental phlegm on pneumonia and bronchitis in early childhood
Lancet
(1974)- et al.
Passive smoking and evolution of lung function in young adults. An 8-year longitudinal study
J. Clin. Epidemiol.
(1995) - et al.
Effect of passive smoking on the development of respiratory symptoms in young adults: an 8-year longitudinal study
J. Clin. Epidemiol.
(1996) - et al.
Smoking, lung function, and α1-antitrypsin deficiency
Lancet
(1985) - et al.
Familial prevalence of chronic obstructive pulmonary disease in a matched pair study
Am. J. Med.
(1977) - et al.
Mis-sense mutation of alpha 1-antichymotrypsin gene associated with chronic lung disease
Lancet
(1992) - et al.
Relationship between dietary vitamin C intake and pulmonary function in the First National Health and Nutrition Examination Survey (NHANES I)
Am. J. Clin. Nutr.
(1994) - et al.
Particulate air pollution and acute health effects
Lancet
(1995) - et al.
Association between polymorphism in gene for microsomal epoxide hydrolase and susceptibility to emphysema
Lancet
(1997) - et al.
Alpha1-antitrypsin deficiency: the clinical and physiological features of pulmonary emphysema in subjects homozygous for Pi type Z
Br. J. Dis. Chest.
(1983)
Long-term ambient concentrations of total suspended particulates, ozone, and sulfur dioxide and respiratory symptoms in a nonsmoking population
Arch. Environ. Health
Molecular genetics of chronic obstructive pulmonary disease
Thorax
Chronic obstructive pulmonary disease
N. Engl. J. Med.
12th Meeting of the Scientific Group on Methodologies for the Safety Evaluation of Chemicals: susceptibility to environmental hazards
Environ. Health Perspect. (Suppl. 4)
Chronic airflow limitation: its relationship to work in dusty occupations
Chest
Occupational exposures: evidence for a causal association with chronic obstructive pulmonary disease
Am. Rev. Respir. Dis.
Alpha1-antitrypsin deficiency in nonsmokers
Am. Rev. Respir. Dis.
Clinical features and history of the destructive lung disease associated with alpha-1-antitrypsin deficiency of adults with pulmonary symptoms
Am. Rev. Respir. Dis.
Dietary antioxidant vitamin intake and lung function in the general population
Am. J. Respir. Crit. Care Med.
Ascorbate deficiency and oxidative stress in the alveolar type II cell
Am. J. Physiol.
Pulmonary function in heterozygotes for alpha1-antitrypsin deficiency: a case-control study
Am. Rev. Respir. Dis.
Diet, lung function, and lung function decline in a cohort of 2512 middle aged men
Thorax
P1 phenotypes and the prevalence of chest symptoms and lung function abnormalities in workers employed in dusty industries
Am. Rev. Respir. Dis.
Environmental tobacco smoke, low birth weight, and hospitalization for respiratory disease
Am. J. Respir. Crit. Care Med.
Cotton dust exposure, across-shift drop in FEV1, and 5-year change in lung function
Am. J. Respir. Crit. Care Med.
Silicosis, chronic airflow limitation, and chronic bronchitis in South African gold miners
Am. Rev. Respir. Dis.
Maternal smoking during pregnancy as a predictor of lung function in children
Am. J. Epidemiol.
Environmental tobacco smoke, wheezing, and asthma in children in 24 communities
Am. J. Respir. Crit. Care Med.
An association between air pollution and mortality in six US cities
N. Engl. J. Med.
Risk factors for childhood asthma and wheezing: importance of maternal and household smoking
Am. J. Respir. Crit. Care Med.
Chronic obstructive pulmonary disease symptom effects of long-term cumulative exposure to ambient levels of total suspended particulates and sulfur dioxide in California Seventh-Day Adventist residents
Arch. Environ. Health
Parental smoking and respiratory illness during early childhood: a 6-year longitudinal study
Pediatr. Pulmonol.
Documentation of ill-health effects of occupational exposure to grain dust through sequential, coherent epidemiologic investigation
Scand. J. Work Environ. Health
Exposure-related declines in the lung function of cotton textile workers
Am. Rev. Respir. Dis.
Acute lower respiratory illness in childhood as a predictor of lung function and chronic respiratory symptoms
Am. Rev. Respir. Dis.
Pulmonary function in Pi M and MZ grainworkers
Chest
Tumor necrosis factor-alpha gene polymorphism in chronic bronchitis
Am. J. Respir. Crit. Care Med.
Genetic and environmental influences on pulmonary function in adult twins
Am. Rev. Respir. Dis.
Glutathione S-transferase P1 (GSTP1) polymorphism in patients with chronic obstructive pulmonary disease [see comments]
Thorax
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