SARS冠状病毒S蛋白候选细胞受体氨基肽酶N的基因变异研究

氨基肽酶N是人类冠状病毒HCoV 2 2 9E的细胞受体 ,可能为SARS冠状病毒 (SARS CoV)S蛋白的受体。应用变性高效液相色谱 (DHPLC)技术筛查了正常无关个体中氨基肽酶N编码基因ANPEP的全部外显子及其两侧部分内含子序列。对筛查中DHPLC峰型提示有基因变异存在的DNA片段行PCR产物直接测序 ,共发现 9种单核苷酸多态 (SNP) ,其中 4种为非同义SNP ,分别为T32 1M(96 2C >T)、S6 5 1L(195 2C >T)、S75 2N(2 2 5 5G >A)和G76 4R(2 2 90G >A) ;其余 5种SNP为T795T(2 385C >T)、IVS7+17G >A、IVS14 16A >G、IVS17+12C >G和IVS17+44C >T。这些SNP的发现 ,为SARS CoV的宿主遗传因素研究 ,特别是发现SARS CoV感染和SARS发病的易感基因或抗病基因 ,提供了遗传标记。

Genomic Variations in the Locus for Aminopeptidase N:A Putative Cellular Receptor for SARS-CoV Spike Glycoprotein

Aminopeptidase N has been identified as the cellular receptor for human coronavirus HCoV 229E and was a putative receptor for the spike glycoprotein encoded by the SARS associated coronavirus (SARS CoV).We report here identification of 9 single nucleotide polymorphisms (SNPs) in ANPEP ,encoding human aminopeptidase N,in Chinese.All ANPEP exons and their flanking intronic sequences were amplified from unrelated normal individuals by polymerase chain reaction (PCR) and screened using denaturing high performance liquid chromatography (DHPLC).Nine SNPs were revealed after direct sequencing of PCR amplified fragments which showed changes of DHPLC chromatogram.Four of these polymorphisms,T321M(962C>T),S651L(1952C>T),S752N(2255G>A) and G764R(2290G>A),were non synonymous;the remaining exonic synonymous and intronic ones were T795T(2385C>T),IVS7+17G>A,IVS14 16A>G,IVS17+12C>G and IVS17+44C>T.Our data may be useful for studies to investigate the role of host genetic factors in SARS pathogenesis,especially for identifying SARS susceptible and/or anti SARS alleles.