Zhang Hongxing, Zhou Gangqiao, Zhi Lianteng, Yang Hao, Zhai Yun, Dong Xiaojia, Zhang Xiumei, Gao Xue, Zhu Yunping, He Fuchu
Department of Genomics and Proteomics, Beijing Institute of Radiation Medicine, Chinese National Human Genome Center at Beijing, and Institute of Biophysics, Chinese Academy of Science, Beijing, China.
J Infect Dis. 2005 Oct 15;192(8):1355-61. doi: 10.1086/491479. Epub 2005 Sep 8.
Genetic determinants of susceptibility to severe acute respiratory syndrome coronavirus (SARS-CoV) infection remain unknown. We assessed whether mannose-binding lectin (MBL) gene polymorphisms were associated with susceptibility to SARS-CoV infection or disease severity in an ethnically homogeneous population born in northern China.
The frequencies of 1 mutation in codon 54 and 3 promoter polymorphisms at nt -550, -221, and 4 were ascertained in 352 patients with SARS and 392 control subjects, by means of polymerase chain reaction direct sequencing.
Of 352 patients with SARS and 392 control subjects, 120 (34.4%) and 91 (23.2%) were carriers of the codon 54 variant, respectively (odds ratio [OR], 1.73 [95% confidence interval {CI}, 1.25-2.39]; P=.00086). A total of 123 (36.0%) of 352 patients with SARS and 100 (25.5%) of 392 control subjects had haplotype pairs associated with medium or low expression of MBL (OR, 1.67 [95% CI, 1.21-2.29]; P=.00187). The population-attributable fraction of patients with SARS that was associated with having the codon 54 variant was 20.1% (95% CI, 7.9%-32.3%).
MBL gene polymorphisms were significantly associated with susceptibility to SARS-CoV infection; this might be explained by the reduced expression of functional MBL secondary to having the codon 54 variant.
严重急性呼吸综合征冠状病毒（SARS-CoV）感染易感性的遗传决定因素尚不清楚。我们评估了甘露糖结合凝集素（MBL）基因多态性与中国北方出生的同种族人群中SARS-CoV感染易感性或疾病严重程度是否相关。
通过聚合酶链反应直接测序，确定了352例SARS患者和392例对照者中第54密码子1种突变以及-550、-221和4位核苷酸处3种启动子多态性的频率。
在352例SARS患者和392例对照者中，分别有120例（34.4%）和91例（23.2%）是第54密码子变异的携带者（优势比[OR]，1.73[95%置信区间{CI}，1.25 - 2.39]；P = 0.00086）。352例SARS患者中有123例（36.0%），392例对照者中有100例（25.5%）具有与MBL中等或低表达相关的单倍型对（OR，1.67[95%CI，1.21 - 2.29]；P = 0.00187）。与第54密码子变异相关的SARS患者人群归因分数为20.1%（95%CI，7.9% - 32.3%）。
MBL基因多态性与SARS-CoV感染易感性显著相关；这可能是由于第54密码子变异导致功能性MBL表达降低所致。
