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What is the evidence of a role for host genetics in susceptibility to influenza A/H5N1?

  • P. HORBY (a1) (a2), H. SUDOYO (a3), V. VIPRAKASIT (a4), A. FOX (a1) (a2), P. Q. THAI (a5), H. YU (a6), S. DAVILA (a7), M. HIBBERD (a7), S. J. DUNSTAN (a1) (a2), Y. MONTEERARAT (a4), J. J. FARRAR (a1) (a2), S. MARZUKI (a3) and N. T. HIEN (a5)...
Abstract
SUMMARY

The apparent family clustering of avian influenza A/H5N1 has led several groups to postulate the existence of a host genetic influence on susceptibility to A/H5N1, yet the role of host factors on the risk of A/H5N1 disease has received remarkably little attention compared to the efforts focused on viral factors. We examined the epidemiological patterns of human A/H5N1 cases, their possible explanations, and the plausibility of a host genetic effect on susceptibility to A/H5N1 infection. The preponderance of familial clustering of cases and the relative lack of non-familial clusters, the occurrence of related cases separated by time and place, and the paucity of cases in some highly exposed groups such as poultry cullers, are consistent with a host genetic effect. Animal models support the biological plausibility of genetic susceptibility to A/H5N1. Although the evidence is circumstantial, host genetic factors are a parsimonious explanation for the unusual epidemiology of human A/H5N1 cases and warrant further investigation.

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Copyright
The online version of this article is published within an Open Access environment subject to the conditions of the Creative Commons Attribution-NonCommercial-ShareAlike licence <http://creativecommons.org/licenses/by-nc-sa/2.5/>. The written permission of Cambridge University Press must be obtained for commercial re-use.
Corresponding author
*Author for correspondence: Dr P. Horby, Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, OxfordOX3 7LJ, UK. (Email: peter.horby@gmail.com)
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