Role of polymorphisms of the inflammatory response genes and DC-SIGNR in genetic susceptibility to SARS and other infections.
1. A genetic risk-association study involving more than 1200 subjects showed individuals homozygous for L-SIGN tandem repeats are less susceptible to SARS infection. 2. This was supported by in vitro binding studies that demonstrated homozygous L-SIGN, compared to heterozygous, had higher binding capacity for SARS coronavirus (SARS-CoV), with higher proteasome-dependent viral degradation. In contrast, homozygous L-SIGN demonstrated lower binding capacity for HIV1-gp120.3. Genetic-association studies for single nucleotide polymorphisms of the inflammatory response genes, namely TNF-alpha, INF-alpha, INF-beta, INF-gamma, IL1-alpha, IL1-beta, IL-4, IL-6 and iNOS, failed to show a significant association with SARS clinical outcomes or susceptibility.
Khoo
U S
US
Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong. uskhoo@pathology.hku.hk
Chan
K Y
KY
Chan
V S
VS
Ching
J C Y
JC
Yam
L
L
Chu
C M
CM
Lai
S T
ST
Wong
T Y
TY
Tam
P
P
Yip
S P
SP
Leung
G M
GM
Lin
C L
CL
Peiris
J S M
JS
D000328:Adult; D000483:Alleles; D000704:Analysis of Variance; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000235:genetics*; D003141:Communicable Diseases / Q000235:genetics / Q000503:physiopathology; D016001:Confidence Intervals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011336:Probability; D011956:Receptors, Cell Surface / Q000235:genetics*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000235:genetics* / Q000378:metabolism; D045169:Severe Acute Respiratory Syndrome / Q000235:genetics* / Q000503:physiopathology; D020080:Tandem Repeat Sequences; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
C433029:CLEC4M protein, human; D015815:Cell Adhesion Molecules; D016207:Cytokines; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha