title: The role of host genetic factors in respiratory tract infectious diseases: systematic review, meta-analyses and field synopsis.
abstract: Host genetic factors have frequently been implicated in respiratory infectious diseases, often with inconsistent results in replication studies. We identified 386 studies from the total of 24,823 studies identified in a systematic search of four bibliographic databases. We performed meta-analyses of studies on tuberculosis, influenza, respiratory syncytial virus, SARS-Coronavirus and pneumonia. One single-nucleotide polymorphism from IL4 gene was significant for pooled respiratory infections (rs2070874; 1.66 [1.29-2.14]). We also detected an association of TLR2 gene with tuberculosis (rs5743708; 3.19 [2.03-5.02]). Subset analyses identified CCL2 as an additional risk factor for tuberculosis (rs1024611; OR = 0.79 [0.72-0.88]). The IL4-TLR2-CCL2 axis could be a highly interesting target for translation towards clinical use. However, this conclusion is based on low credibility of evidence - almost 95% of all identified studies had strong risk of bias or confounding. Future studies must build upon larger-scale collaborations, but also strictly adhere to the highest evidence-based principles in study design, in order to reduce research waste and provide clinically translatable evidence.
authors.affiliation: Department of Public Health, University of Split School of Medicine, Split, Croatia.
authors.forename: Inga
authors.initials: I
authors.lastname: Patarčić
authors.affiliation: Department of Public Health, University of Split School of Medicine, Split, Croatia.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gelemanović
authors.affiliation: Department of Public Health, University of Split School of Medicine, Split, Croatia.
authors.forename: Mirna
authors.initials: M
authors.lastname: Kirin
authors.affiliation: Department of Public Health, University of Split School of Medicine, Split, Croatia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Kolčić
authors.affiliation: Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics , University of Edinburgh, Edinburgh, UK.
authors.forename: Evropi
authors.initials: E
authors.lastname: Theodoratou
authors.affiliation: Roslin Institute, University of Edinburgh, Midlothian, UK.|Intensive Care Unit, Royal Infirmary of Edinburgh, Edinburgh, UK.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Baillie
authors.affiliation: Department of Medical Microbiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Menno D
authors.initials: MD
authors.lastname: de Jong
authors.affiliation: Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics , University of Edinburgh, Edinburgh, UK.
authors.forename: Igor
authors.initials: I
authors.lastname: Rudan
authors.affiliation: Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics , University of Edinburgh, Edinburgh, UK.
authors.forename: Harry
authors.initials: H
authors.lastname: Campbell
authors.affiliation: Department of Public Health, University of Split School of Medicine, Split, Croatia.|Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics , University of Edinburgh, Edinburgh, UK.
authors.forename: Ozren
authors.initials: O
authors.lastname: Polašek
mesh_terms: D018932:Chemokine CCL2 / Q000235:genetics; D016208:Databases, Factual; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012141:Respiratory Tract Infections / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051195:Toll-Like Receptor 2 / Q000235:genetics; D014376:Tuberculosis / Q000235:genetics / Q000401:mortality / Q000473:pathology
chemical_list: D018932:Chemokine CCL2; D051195:Toll-Like Receptor 2; D015847:Interleukin-4