Angiotensin-converting enzyme genotype and late respiratory complications of mustard gas exposure

BACKGROUND: Exposure to mustard gas frequently results in long-term respiratory complications. However the factors which drive the development and progression of these complications remain unclear. The Renin Angiotensin System (RAS) has been implicated in lung inflammatory and fibrotic responses. Genetic variation within the gene coding for the Angiotensin Converting Enzyme (ACE), specifically the Insertion/Deletion polymorphism (I/D), is associated with variable levels of ACE and with the severity of several acute and chronic respiratory diseases. We hypothesized that the ACE genotype might influence the severity of late respiratory complications of mustard gas exposure. METHODS: 208 Kurdish patients who had suffered high exposure to mustard gas, as defined by cutaneous lesions at initial assessment, in Sardasht, Iran on June 29 1987, underwent clinical examination, spirometric evaluation and ACE Insertion/Deletion genotyping in September 2005. RESULTS: ACE genotype was determined in 207 subjects. As a continuous variable, FEV(1 )% predicted tended to be higher in association with the D allele 68.03 ± 20.5%, 69.4 ± 21.4% and 74.8 ± 20.1% for II, ID and DD genotypes respectively. Median FEV(1 )% predicted was 73 and this was taken as a cut off between groups defined as having better or worse lung function. The ACE DD genotype was overrepresented in the better spirometry group (Chi(2 )4.9 p = 0.03). Increasing age at the time of exposure was associated with reduced FEV(1 )%predicted (p = 0.001), whereas gender was not (p = 0.43). CONCLUSION: The ACE D allele is associated with higher FEV(1 )% predicted when assessed 18 years after high exposure to mustard gas.