Hamano Emi, Hijikata Minako, Itoyama Satoru, Quy Tran, Phi Nguyen Chi, Long Hoang Thuy, Ha Le Dang, Ban Vo Van, Matsushita Ikumi, Yanai Hideki, Kirikae Fumiko, Kirikae Teruo, Kuratsuji Tadatoshi, Sasazuki Takehiko, Keicho Naoto
Department of Respiratory Diseases, Research Institute, International Medical Center of Japan, Japan.
Biochem Biophys Res Commun. 2005 Apr 22;329(4):1234-9. doi: 10.1016/j.bbrc.2005.02.101.
We hypothesized that host antiviral genes induced by type I interferons might affect the natural course of severe acute respiratory syndrome (SARS). We analyzed single nucleotide polymorphisms (SNPs) of 2',5'-oligoadenylate synthetase 1 (OAS-1), myxovirus resistance-A (MxA), and double-stranded RNA-dependent protein kinase in 44 Vietnamese SARS patients with 103 controls. The G-allele of non-synonymous A/G SNP in exon 3 of OAS-1 gene showed association with SARS (p=0.0090). The G-allele in exon 3 of OAS-1 and the one in exon 6 were in strong linkage disequilibrium and both of them were associated with SARS infection. The GG genotype and G-allele of G/T SNP at position -88 in the MxA gene promoter were found more frequently in hypoxemic group than in non-hypoxemic group of SARS (p=0.0195). Our findings suggest that polymorphisms of two IFN-inducible genes OAS-1 and MxA might affect susceptibility to the disease and progression of SARS at each level.
我们推测，I型干扰素诱导的宿主抗病毒基因可能会影响严重急性呼吸综合征（SARS）的自然病程。我们分析了44例越南SARS患者和103名对照者的2',5'-寡腺苷酸合成酶1（OAS-1）、黏液病毒抗性A（MxA）以及双链RNA依赖性蛋白激酶的单核苷酸多态性（SNP）。OAS-1基因第3外显子非同义A/G SNP的G等位基因与SARS相关（p = 0.0090）。OAS-1基因第3外显子的G等位基因与第6外显子的G等位基因处于强连锁不平衡状态，且二者均与SARS感染相关。在SARS的低氧血症组中，MxA基因启动子-88位G/T SNP的GG基因型和G等位基因比非低氧血症组更常见（p = 0.0195）。我们的研究结果表明，两种I型干扰素诱导基因OAS-1和MxA的多态性可能在各个层面影响对该疾病的易感性以及SARS的病程。
