Current progress in pneumonia research

Introduction

Diagnosis and treatment of acute pneumonia (Pn) is a problem of high significance in modern medicine. The incidence of complicated and lethal acute Pn has increased [1]. Candidate genes are of great importance in the course of acute diseases and their complications. Cytokines and xenobiotic detoxication genes are the most investigated. The aim of the investigation was to study genetic predisposition to acute Pn.

Methods

Results of the associative DNA polymorphism studies in 243 patients with acute community-acquired Pn are presented; 178 healthy individuals formed a control group. Genetic variability of the candidate loci was studied: renin-angiotensin ACE system gene, chemokine receptor CCR5 gene and four genes controlling xenobiotic detoxification (CYP1A1, GSTM1, GSTT1, GSTP1). Multiplex polymerase chain reaction was utilized for genotyping of insertion-deletion polymorphism on loci ACE (287 nucleotide pairs) and CCR5 (deletion of 32 nucleotide pairs). The odds ratio index was used to describe the degree of association of the genotypes with the diseases. Statistical analysis was done by means of Fisher's exact test and the online program SNPStats http://bioinfo.iconcologia.net.

Results

An increased predisposition to Pn development was registered in homozygotes in deletion at the ACE locus (OR = 1.8; P = 0.013), positive genotypes of the GSTM1 locus (OR = 1.7; P = 0.010) and homozygotes in allele 606T of the CYP1A1 gene (OR = 1.6; P = 0.020).

Conclusions

A combination of positive genotypes of the GSTM1 locus and homozygotes in allele 606T of the CYP1A1 gene (OR = 1.9, P = 0.006; incidence in controls >20%) presented with a most effective prognostic power.