title: Host genetic risk factors for community-acquired pneumonia.
abstract: This study was conducted to establish the contribution of genetic host factors in the susceptibility to community acquired pneumonia (CAP) in the Russian population. Patients with CAP (n=334), volunteers without a previous history of CAP, constantly exposed to infectious agents, control A group (n=141) and a second control group B consisted of healthy persons (n=314) were included in the study. All subjects were genotyped for 13 polymorphic variants in the genes of xenobiotics detoxification CYP1A1 (rs2606345, rs4646903, and rs1048943), GSTM1 (Ins/del), GSTT1 (Ins/del), ABCB1 rs1045642); immune and inflammation response IL-6 (rs1800795), TNF-a (rs1800629), MBL2 (rs7096206), CCR5 (rs333), NOS3 (rs1799983), angiotensin-converting enzyme ACE (rs4340), and occlusive vascular disease/hyperhomocysteinemia MTHFR (rs1801133). Seven polymorphic variants in genes CYP1A1, GSTM1, ABCB1, NOS3, IL6, CCR5 and ACE were associated with CAP. For two genes CYP1A1 and GSTM1 associations remained significant after correction for multiple comparisons. Multiple analysis by the number of all risk genotypes showed a highly significant association with CAP (P=2.4×10(-7), OR=3.03, 95% CI 1.98-4.64) with the threshold for three risk genotypes. Using the ROC-analysis, the AUC value for multi-locus model was estimated as 68.38.
authors.affiliation: N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, 3 Gubkin Street, Moscow 117971, Russia. salnikovalyubov@gmail.com
authors.forename: Lyubov E
authors.initials: LE
authors.lastname: Salnikova
authors.forename: Tamara V
authors.initials: TV
authors.lastname: Smelaya
authors.forename: Viktor V
authors.initials: VV
authors.lastname: Moroz
authors.forename: Arkady M
authors.initials: AM
authors.lastname: Golubev
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Rubanovich
mesh_terms: D000328:Adult; D017714:Community-Acquired Infections / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics*; D008297:Male; D011014:Pneumonia / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012426:Russia; D055815:Young Adult
chemical_list: D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase