Association between Mannose-Binding Lectin Gene Polymorphisms and Susceptibility to Severe Acute Respiratory Syndrome Coronavirus Infection

Hongxing Zhang 0 1 2 3 Gangqiao Zhou () 1 2 3 Lianteng Zhi 1 2 3 Hao Yang 1 2 3 Yun Zhai 1 2 3 Xiaojia Dong 1 2 Xiumei Zhang 1 2 Xue Gao 2 3 Yunping Zhu 2 3 Fuchu He 1 2 3 4 0 Institute of Biophysics, Chinese Academy of Science , Beijing 1 Chinese National Human Genome Center at Beijing 2 Received 9 March 2005; accepted 31 May 2005; electronically published 8 September 2005. Potential conflicts of interest: none reported. Financial support: Chinese High-Tech Program (grants 2001AA224011 and 2002BA711A10); Medicine and Health Research Program (grant 01Z018); Chinese National Science Fund for Creative Research Groups (grant 30321003). Beijing Institute of Radiation Medicine , 27 Tai-Ping Rd., 100850 Beijing, China 3 Department of Genomics and Proteomics, Beijing Institute of Radiation Medicine 4 Institute of Biomedical Sciences, Fudan University , Shanghai, China Background. Genetic determinants of susceptibility to severe acute respiratory syndrome coronavirus (SARSCoV) 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. Methods. 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. Results. 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 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 p .00187). The populationattributable fraction of patients with SARS that was associated with having the codon 54 variant was 20.1% (95% CI, 7.9%-32.3%). Conclusions. 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. - RESULTS Polymorphism 596CrT 550GrC (H/L) 435GrA 427ArC 349ArG 336ArG 329 to 324 I/D 221GrC (Y/X) 70CrT 4CrT (P/Q) 223CrT (A/D, codon 52) 230GrA (A/B, codon 54) 239GrA (A/C, codon 57) 366GrA Position(s)a Minor-allele frequency 50 96 Region Promoter Promoter Promoter Promoter Promoter Promoter Promoter Promoter Promoter 5 UTR Exon1 Exon1 Exon1 Intron1 DISCUSSION Acknowledgment (...truncated)