Genetics and pulmonary medicine bullet 9: Molecular genetics of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a major cause of ill health and is increasing in many parts of the world. It is one of the commonest causes of death and the only common cause of death which is increasing. COPD is characterised by a slowly progressive irreversible airflow obstruction that is due to a loss of lung elasticity resulting from parenchymal destruction and peripheral airflow obstruction. Cigarette smoking is currently a causal factor in more than 90% of patients in westernised societies, so environmental factors are clearly very important in the disease.1However, in Caucasians only 10–20% of chronic heavy cigarette smokers develop symptomatic COPD, suggesting that genetic factors are likely to be important in determining which cigarette smokers are at risk from developing airflow obstruction. Furthermore, some patients develop airflow obstruction at an earlier age, again suggesting that genetic factors may determine the progression of COPD. Patients who have a genetic deficiency in the anti-protease α1-antitrypsin (α1-AT) have a very high risk of developing emphysema at an early age if they smoke, indicating the importance of genetic factors in some patients with COPD. Despite the clinical importance of COPD, relatively few studies have searched for genetic factors using modern molecular genetic techniques. There may also be differences in the prevalence of COPD in different ethnic groups, but these are difficult to separate from lifestyle factors. For example, the prevalence of COPD is apparently low in China and this cannot be entirely accounted for by a lower tobacco consumption.2 Anecdotally, COPD is uncommon in Chinese living in the USA which suggests that there may be genetic differences in the factors that protect against COPD. In Hawaii, the prevalence of COPD in Japanese-Americans smoking more than 20 cigarettes daily was 7.9% compared with 16.7% …