Genetic Predisposition to the Development of Acute Community-Acquired Pneumonia

Abstract

Objective: to study associations of DNA polymorphism in acute community-acquired pneumonia (ACAP). Subjects and methods. The study enrolled 243 patients with ACAP; a control group included 178 healthy individuals. Genetic variability was investigated for the following candidate locuses: the ACE renin-angiotensin system gene, the CCR5 chemokine receptor gene and 4 xenobiotic detoxification genes (CYP1A1, CSTM1, GSTT1, and GSTP1). According to the earlier data on the effect of CYP1A1 alleles on predisposition to pneumonia, haplotypes were determined by 3 polymorphic sites of this gene. Results. Protective and predisposing geno- and haplotypes were described by the above loci and their combinations. Homozygotes for the deletion at the ACE locus (OR=1.8; p=0.013); GSTM1-pos-itive genotypes (OR=1.7; p=0.010) and homozygotes for 606T allele in the CYP1A1 gene (OR=1.6; p=0.020) were found to have a higher predisposition to pneumonia. A combination of the two latter genotypes (OR=1.9 at p=0.006; its frequency in the control was more than 20%) proved to be prognostically most effective. Conclusion: three polymorphic markers were identified in the CYP1A1, GSTM1, and ACE genes associated with the development and course of ACAP. Key words: gene polymorphism, xenobiotic detoxification genes, pneumonia.