Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The persistent mortality from community-acquired pneumonia may be explained by genetic predisposition. Specific mutations or polymorphisms in host response genes that are associated with adverse outcomes from infection can be grouped into four categories: antigen recognition, proinflammatory responses, anti-inflammatory responses, and effector mechanisms. Mannose-binding lectin polymorphisms have a more dominant role in pneumonia when compared with other pattern recognition molecules such as the toll-like receptors. The roles of TNF and lymphotoxin alpha polymorphisms remain unclear despite extensive study. IL-10 and IL-1 receptor antagonist polymorphisms have an important role in the anti-inflammatory response. Specific organ dysfunction, such as ARDS or DIC, may be related to polymorphisms in specific effector genes.
 ...
PMID:Genetic susceptibility to pneumonia. 1580 63

The variable clinical presentation of community-acquired pneumonia (CAP) suggests a genetic predisposition. Specific mutations or polymorphisms in host response genes such as pattern recognition molecules (PRMs), inflammatory molecules, and the coagulation system are likely to play a role in this variable response to CAP. Mannose-binding lectin polymorphisms appear to play a more dominant role in CAP than other PRMs, such as the Toll-like receptors (TLRs). The role of tumor necrosis factor (TNF) and lymphotoxin alpha (LTA) polymorphisms remain unclear despite extensive study whereas interleukin (IL)-10 and IL-1 receptor antagonist polymorphisms appear to play an important role in the anti-inflammatory response. Coagulation gene polymorphisms are likely important as well. The real value of these genetic studies in CAP and other severe infections will be when the management of an individual patient can be optimized by therapy based on the individual's genotype for molecules important in outcome.
 ...
PMID:Genetics of community-acquired pneumonia. 1638 27

Polymorphisms in the central major histocompatibility complex (MHC) (particularly TNF and adjacent genes) associate with several immunopathological diseases and with susceptibility to pneumonia. The MHC is characterised by strong linkage disequilibrium (LD), so identification of loci affecting disease must be based on haplotypes. We have defined 31 tumour necrosis factor (TNF) block haplotypes (denoted FV1-31) in Caucasians, Asians and Australian Aboriginals. This study correlates the carriage of TNF block haplotypes with TNF and lymphotoxin alpha (LTA) protein production by peripheral blood mononuclear cells from 205 healthy Caucasian subjects, following in vitro stimulation with Streptococcus pneumoniae (S. pneumoniae; gram-positive bacteria), Escherichia coli (E. coli; gram-negative bacteria) or TNF over 4, 8 and 24 h. Fifteen haplotypes were present at >1%, accounting for 94.5% of the cohort. The haplotypes were grouped into five families based on common alleles. Following stimulation, cells from carriers of the FV10 haplotype (family 2) produced less LTA compared with non-FV10 carriers. Carriers of the FV18 haplotype (family 4) produced more LTA than other donors. Induction of TNF by S. pneumoniae following 24 h stimulation was also greater in donors with FV18. The FV18 haplotype associated with the 44.1 MHC ancestral haplotype (HLA-A2, -C5, -B44, -DRB1*0401 and -DQB1*0301) that has few disease associations. FV16 occurred in the 8.1 MHC haplotype (HLA-A2, B8, DR3) that is associated with multiple immunopathological diseases. FV16 did not affect TNF or LTA levels. The findings suggest that many genetic variations critical in vivo are not effectively modelled by short-term cultures.
 ...
PMID:Characterisation of TNF block haplotypes affecting the production of TNF and LTA. 2121 21