CD209 (DC-SIGN) -336A>G promoter polymorphism and severe acute respiratory syndrome in Hong Kong Chinese.
CD209 (DC-SIGN) is an important C-type lectin which acts a receptor of many pathogens. The single nucleotide polymorphism (SNP) -336A>G in the CD209 promoter has been demonstrated to regulate promoter activity and to be associated with several important infectious diseases, such as human immunodeficiency virus-1 (HIV-1), Mycobacterium tuberculosis, and Dengue fever. CD209 facilitates severe acute respiratory syndrome (SARS)-coronavirus spike protein-bearing pseudotype driven infection of permissive cells in vitro. In keeping with previously published findings, our in vitro studies confirmed that this SNP modulates gene promoter activity. Genetic association analysis of this SNP with clinico-pathologic outcomes in 824 serologic confirmed SARS patients showed that the -336AG/GG genotype SARS patients was associated with lower standardized lactate-dehydrogenase (LDH) levels compared with the -336AA patients (p = 0.014, odds ratio = 0.40). High LDH levels are known to be an independent predictor for poor clinical outcome, probably related to tissue destruction from immune hyperactivity. Hence, SARS patients with the CD209 -336 AA genotype carry a 60% chance of having a poorer prognosis. This association is in keeping with the role of CD209 in modulating immune response to viral infection. The relevance of these findings for other infectious diseases and inflammatory conditions would be worth investigating.
Chan
Kelvin Yuen Kwong
KY
Department of Pathology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China.
Xu
Mei-Shu
MS
Ching
Johannes Chi Yun
JC
So
Thomas Man Kit
TM
Lai
Sik-To
ST
Chu
Chung-Ming
CM
Yam
Loretta Y C
LY
Wong
Andrew T Y
AT
Chung
Pui Hong
PH
Chan
Vera Sau Fong
VS
Lin
Chen Lung Steve
CL
Sham
Pak Chung
PC
Leung
Gabriel M
GM
Peiris
Joseph S M
JS
Khoo
Ui-Soon
US
D000328:Adult; D015703:Antigens, CD / Q000235:genetics; D044466:Asian People / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D015342:DNA Probes / Q000235:genetics; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006367:HeLa Cells; D006579:Heterozygote; D006720:Homozygote; D006723:Hong Kong; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood; D037181:Lectins, C-Type / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D045169:Severe Acute Respiratory Syndrome / Q000097:blood / Q000235:genetics*; D016329:Sp1 Transcription Factor / Q000235:genetics; D050656:Transcription Factor AP-2 / Q000235:genetics; D014162:Transfection; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D004247:DNA; D015342:DNA Probes; D007770:L-Lactate Dehydrogenase; D037181:Lectins, C-Type; D009687:Nuclear Proteins; D011956:Receptors, Cell Surface; D016329:Sp1 Transcription Factor; D050656:Transcription Factor AP-2; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C483616:ICAM3 protein, human