Genetic risk of acute pulmonary infections and sepsis

Abstract

The focus of this review is the genetic influence on pneumonia and sepsis. A large number of polymorphisms in a diverse collection of genes have been identified as potential candidates to explain the genetic variability in susceptibility to acute pulmonary infection and its adverse outcomes. Unfortunately, apart from polymorphisms in mannose-binding lectin, CD14 and the IgG2 receptor, there is little consensus on which polymorphisms are truly important. As well as discussing some of the major published findings, this review will focus on the reasons for failure to make more progress. We will also address the issues for future research, particularly the need to address the limitations of past studies, including the grouping of patients with different pathogens, as the relationship between genotype and phenotype may be highly pathogen dependent. Finally, our approach to reporting genetic studies needs to change to minimize the number of publications of spurious findings.

Keywords::

• genetic risk
• pneumonia
• polymorphisms
• sepsis

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Notes

ACE: Angiotensin-converting enzyme; CXCL: Chemokine (C–X–C motif) ligand; IRAK: IL-1 receptor-associated kinase; MAL: Myeloid-differentiation factor 88 adapter-like protein; NEMO: NF-κB essential modulator; NFKBIZ: Nuclear factor of κ light polypeptide gene enhancer in B cells inhibitor; NOD: Nucleotide-binding oligomerization domain; TLR: Toll-like receptor.