2003年SARS在全球爆發(fā)時,,不同的個體在感染后表現(xiàn)出不同的病程和最終的治療結(jié)果,,這被認(rèn)為是個體本身的遺傳因素在這個過程中起了一定的作用,,即不同個體在一些基因上的多態(tài)影響了他們對一些疾病的易感性。CD209L基因是19號染色體上C型凝集素家族中的一員,它被證明是SARS病毒的受體,并且它的第4外顯子的VNTR多態(tài)被認(rèn)為和宿主對病毒的易感性有關(guān),。但是這個結(jié)論在其后其他兩個研究小組的工作未被得到證實。
為了深入探討這個問題,在中國科學(xué)院昆明動物研究所-香港中文大學(xué)生物資源與疾病分子機理聯(lián)合實驗室張亞平院士和鄧亮生教授的共同指導(dǎo)下,,博士生李慧等對19號染色體上C型凝集素家族的4個成員(FCER2,, CLEC4G, CD209 和 CD209L)作了全面的研究,,采用檢測tagSNPs的方法,,在C型凝集素家族基因簇上選取了23個tagSNPs位點來代表這個基因簇的多態(tài)。檢測了來自中國香港的181個SARS病人和172個匹配的正常對照,,結(jié)果表明C型凝集素家族的4個基因與中國南方漢族群體對SARS病毒的易感之間沒有相關(guān)性,。同時檢測了來自中國不同地區(qū)的1145個漢族樣本CD209L基因VNTR的多態(tài)分布情況,結(jié)果表明這個位點在中國人群中存在群體分層現(xiàn)象,,提示之前的研究小組可能得到了假陽性結(jié)果,主要原因可能正是由于他們忽略了這個問題,。
該研究成果發(fā)表于《醫(yī)學(xué)遺傳學(xué)雜志》(Journal of Medical Genetics)上,。(生物谷Bioon.com)
生物谷推薦原始出處:
Journal of Medical Genetics,doi:10.1136/jmg.2008.058966,,Hui Li,,Ya-Ping Zhang
Polymorphisms in the C-type Lectin Genes Cluster in Chromosome 19 and Predisposition to SARS-Coronavirus Infection
Hui Li 1, Nelson L S Tang 2 and Ya-Ping Zhang 1*
1 Kunming Institue of Zoology, CAS, China
2 The Chinese University of Hong Kong, Hong Kong
Polymorphisms of CLEC4M had been associated with predisposition for infection by the SAR-CoV virus. DC-SIGNR, a C-type lectin encoded by CLEC4M, is a receptor for the virus. A VNTR polymorphism in its neck region was recently associated with susceptibility to SARS infection. However, this association was controversial and was not supported by subsequent studies. Two explanations may account for this discrepancy: (1) there may be an unknown predisposition polymorphism located in the proximity which is linked to the VNTR, or (2) it was a spurious association due to unrecognized population structure in the VNTR. We performed a comprehensively genetic association study on this C-type lectin gene cluster (FCER2, CLEC4G, CD209, and CLEC4M) at 19p13.3 by a tagging SNPs approach. 23 tagSNPs were genotyped in 181 SARS patients and 172 population controls. No significant association with disease predisposition was detected. Genetic variations in this cluster also did not predict disease prognosis. But we detected a population stratification of the VNTR alleles in a sample of 1145 Han Chinese collected from different part of China. The results indicated that genetic predisposition allele was not found in this lectin gene cluster and population stratification might cause the previous positive association.