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Sci Rep. 2015 Nov 3;5:16119. doi: 10.1038/srep16119.

The role of host genetic factors in respiratory tract infectious diseases: systematic review, meta-analyses and field synopsis.

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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.
Roslin Institute, University of Edinburgh, Midlothian, UK.
Intensive Care Unit, Royal Infirmary of Edinburgh, Edinburgh, UK.
Department of Medical Microbiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.


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.

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