title: Genetic dissection of host immune response in pneumonia development and progression.
abstract: The role of host genetic variation in pneumonia development and outcome is poorly understood. We studied common polymorphisms in the genes of proinflammatory cytokines (IL6 rs1800795, IL8 rs4073, IL1B rs16944), anti-inflammatory cytokines (IL10 rs1800896, IL4 rs2243250, IL13 rs20541) and toll-like receptors (TLR2 rs5743708 and rs4696480, TLR4 rs4986791, TLR9 rs352139, rs5743836 and rs187084) in patients with community-acquired pneumonia (CAP) (390 cases, 203 controls) and nosocomial pneumonia (355 cases, 216 controls). Experimental data were included in a series of 11 meta-analyses and eight subset analyses related to pneumonia susceptibility and outcome. TLR2 rs5743708 minor genotype appeared to be associated with CAP/Legionnaires' disease/pneumococcal disease. In CAP patients, the IL6 rs1800795-C allele was associated with severe sepsis/septic shock/severe systemic inflammatory response, while the IL10 rs1800896-A allele protected against the development of these critical conditions. To contribute to deciphering of the above results, we performed an in silico analysis and a qualitative synthesis of literature data addressing basal and stimulated genotype-specific expression level. This data together with database information on transcription factors' affinity changes caused by SNPs in putative promoter regions, the results of linkage disequilibrium analysis along with SNPs functional annotations supported assumptions about the complexity underlying the revealed associations.
authors.affiliation: V. A. Negovsky Research Institute of General Reanimatology, Russian Academy of Sciences, 25 Petrovka str., build.2, Moscow 107031, Russia.
authors.forename: Tamara V
authors.initials: TV
authors.lastname: Smelaya
authors.affiliation: N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, 3 Gubkin street, Moscow 117971, Russia.
authors.forename: Olesya B
authors.initials: OB
authors.lastname: Belopolskaya
authors.affiliation: N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, 3 Gubkin street, Moscow 117971, Russia.
authors.forename: Svetlana V
authors.initials: SV
authors.lastname: Smirnova
authors.affiliation: V. A. Negovsky Research Institute of General Reanimatology, Russian Academy of Sciences, 25 Petrovka str., build.2, Moscow 107031, Russia.
authors.forename: Artem N
authors.initials: AN
authors.lastname: Kuzovlev
authors.affiliation: V. A. Negovsky Research Institute of General Reanimatology, Russian Academy of Sciences, 25 Petrovka str., build.2, Moscow 107031, Russia.
authors.forename: Viktor V
authors.initials: VV
authors.lastname: Moroz
authors.affiliation: V. A. Negovsky Research Institute of General Reanimatology, Russian Academy of Sciences, 25 Petrovka str., build.2, Moscow 107031, Russia.
authors.forename: Arkadiy M
authors.initials: AM
authors.lastname: Golubev
authors.affiliation: Center for Research and Development, Angeles University Foundation, Angeles City 2009, Philippines.
authors.forename: Noel A
authors.initials: NA
authors.lastname: Pabalan
authors.affiliation: V. A. Negovsky Research Institute of General Reanimatology, Russian Academy of Sciences, 25 Petrovka str., build.2, Moscow 107031, Russia.|N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, 3 Gubkin street, Moscow 117971, Russia.
authors.forename: Lyubov E
authors.initials: LE
authors.lastname: Salnikova
mesh_terms: D017714:Community-Acquired Infections / Q000235:genetics*; D003198:Computer Simulation; D003428:Cross Infection / Q000235:genetics*; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D007877:Legionnaires' Disease / Q000235:genetics*; D015810:Linkage Disequilibrium; D011014:Pneumonia / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics
chemical_list: C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D014157:Transcription Factors; D016753:Interleukin-10