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, FEV1 % 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 FEV1 % 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 (Chi2 4.9 p = 0.03). Increasing age at the time of exposure was associated with reduced FEV1 %predicted (p = 0.001), whereas gender was not (p = 0.43).


CONCLUSIONS
The ACE D allele is associated with higher FEV1 % predicted when assessed 18 years after high exposure to mustard gas.
Hosseini-Khalili
Ali Reza
AR
UCL Institute for Human Health and Performance, Ground Floor, Charterhouse Building, UCL Archway Campus, Highgate Hill, Archway, London N19 5LW, UK. alireza_hosseini50@yahoo.com
Thompson
Julian
J
Kehoe
Anthony
A
Hopkinson
Nicholas S
NS
Khoshbaten
A
A
Soroush
Mohammad Reza
MR
Humphries
Steve E
SE
Montgomery
Hugh
H
Ghanei
Mostafa
M
D000328:Adult; D002618:Chemical Warfare; D002619:Chemical Warfare Agents / Q000009:adverse effects*; D004781:Environmental Exposure; D005260:Female; D005541:Forced Expiratory Volume; D017353:Gene Deletion; D006801:Humans; D007492:Iran; D007493:Iraq; D008171:Lung Diseases / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D009151:Mustard Gas / Q000009:adverse effects*; D011110:Polymorphism, Genetic; D012083:Renin / Q000235:genetics*; D013147:Spirometry
D002619:Chemical Warfare Agents; D012083:Renin; D009151:Mustard Gas