Human Genetic Variation Influences Enteric Fever Progression.


Ma PY(1), Tan JE(2), Hee EW(2), Yong DWX(2), Heng YS(2), Low WX(2), Wu XH(2), Cletus C(2), Kumar Chellappan D(3), Aung K(4), Yong CY(5), Liew YK(3).
Author information:
(1)School of Postgraduate Studies, International Medical University, Bukit Jalil, Kuala Lumpur 57000, Malaysia.
(2)School of Pharmacy, International Medical University, Kuala Lumpur 57000, Malaysia.
(3)Department of Life Sciences, International Medical University, Kuala Lumpur 57000, Malaysia.
(4)Department of Pathology, International Medical University, Kuala Lumpur 57000, Malaysia.
(5)Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Selangor 43400, Malaysia.


In the 21st century, enteric fever is still causing a significant number of mortalities, especially in high-risk regions of the world. Genetic studies involving the genome and transcriptome have revealed a broad set of candidate genetic polymorphisms associated with susceptibility to and the severity of enteric fever. This review attempted to explain and discuss the past and the most recent findings on human genetic variants affecting the progression of Salmonella typhoidal species infection, particularly toll-like receptor (TLR) 4, TLR5, interleukin (IL-) 4, natural resistance-associated macrophage protein 1 (NRAMP1), VAC14, PARK2/PACRG, cystic fibrosis transmembrane conductance regulator (CFTR), major-histocompatibility-complex (MHC) class II and class III. These polymorphisms on disease susceptibility or progression in patients could be related to multiple mechanisms in eliminating both intracellular and extracellular Salmonella typhoidal species. Here, we also highlighted the limitations in the studies reported, which led to inconclusive results in association studies. Nevertheless, the knowledge obtained through this review may shed some light on the development of risk prediction tools, novel therapies as well as strategies towards developing a personalised typhoid vaccine.