Association of SARS susceptibility with single nucleic acid polymorphisms of OAS1 and MxA genes: a case-control study.
BACKGROUND
Host genetic factors may play a role in susceptibility and resistance to SARS associated coronavirus (SARS-CoV) infection. The study was carried out to investigate the association between the genetic polymorphisms of 2',5'-oligoadenylate synthetase 1 (OAS1) gene as well as myxovirus resistance 1 (MxA) gene and susceptibility to SARS in Chinese Han population.


METHODS
A hospital-based case-control study was conducted. A collective of 66 SARS cases and 64 close contact uninfected controls were enrolled in this study. End point real time polymerase chain reaction (PCR) and PCR-based Restriction Fragment Length Polymorphism (RFLP) analysis were used to detect the single nucleic polymorphisms (SNPs) in OAS1 and MxA genes. Information on other factors associated with SARS infection was collected using a pre-tested questionnaire. Univariate and multivariate logistic analyses were conducted.


RESULTS
One polymorphism in the 3'-untranslated region (3'-UTR) of the OAS1 gene was associated with SARS infection. Compared to AA genotype, AG and GG genotypes were found associated with a protective effect on SARS infection with ORs (95% CI) of 0.42 (0.20-0.89) and 0.30 (0.09-0.97), respectively. Also, a GT genotype at position 88 in the MxA gene promoter was associated with increased susceptibility to SARS infection compared to a GG genotype (OR = 3.06, 95% CI: 1.25-7.50). The associations of AG genotype in OAS1 and GT genotype in MxA remained significant in multivariate analyses after adjusting for SARS protective measures (OR = 0.38, 95% CI: 0.14-0.98 and OR = 3.22, 95% CI: 1.13-9.18, respectively).


CONCLUSIONS
SNPs in the OAS1 3'-UTR and MxA promoter region appear associated with host susceptibility to SARS in Chinese Han population.
He
Jing
J
Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing, China. jinghe2004@gmail.com
Feng
Dan
D
de Vlas
Sake J
SJ
Wang
Hongwei
H
Fontanet
Arnaud
A
Zhang
Panhe
P
Plancoulaine
Sabine
S
Tang
Fang
F
Zhan
Lin
L
Yang
Hong
H
Wang
Tianbao
T
Richardus
Jan H
JH
Habbema
J Dik F
JD
Cao
Wuchun
W
D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics*; D000328:Adult; D000704:Analysis of Variance; D016022:Case-Control Studies; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D064547:Myxovirus Resistance Proteins; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D045169:Severe Acute Respiratory Syndrome / Q000235:genetics*
C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; C475085:OAS1 protein, human; D015088:2',5'-Oligoadenylate Synthetase; D019204:GTP-Binding Proteins