What is the evidence of a role for host genetics in susceptibility to influenza A/H5N1?
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.
Horby
P
P
Oxford University Clinical Research Unit, Vietnam. peter.horby@gmail.com
Sudoyo
H
H
Viprakasit
V
V
Fox
A
A
Thai
P Q
PQ
Yu
H
H
Davila
S
S
Hibberd
M
M
Dunstan
S J
SJ
Monteerarat
Y
Y
Farrar
J J
JJ
Marzuki
S
S
Hien
N T
NT
D016000:Cluster Analysis; D020022:Genetic Predisposition to Disease; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype; D007251:Influenza, Human / Q000235:genetics* / Q000635:transmission / Q000821:virology*; D010375:Pedigree; D012307:Risk Factors