{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T23:28:06Z","timestamp":1790724486939,"version":"4.1.0"},"reference-count":47,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2019,4,25]],"date-time":"2019-04-25T00:00:00Z","timestamp":1556150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014996","name":"Health Commission of Zhejiang Province","doi-asserted-by":"publisher","award":["2019ZD003"],"award-info":[{"award-number":["2019ZD003"]}],"id":[{"id":"10.13039\/501100014996","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Objective: This study was conducted to identify the association between rs4804803 polymorphism in DC-SIGN with the susceptibility of severe dengue. Methods: A comprehensive search was conducted to identify all eligible papers in PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Google Scholar. Odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were used to assess the association. Subgroup analyses were performed by ethnicity. Sensitivity analyses were performed through employing different statistical models (fixed versus random effect model). Results: A total of nine papers and 12 studies, with 1520 severe dengue and 1496 clinical dengue infection were included. The overall meta-analysis revealed significant associations between rs4804803 and severe dengue under the recession (GG versus GA\/AA: OR = 0.44, 95%CI, 0.23\u20130.82) and a codominant model (GG versus AA: OR = 0.43, 95%CI, 0.23\u20130.81), but sensitivity analysis indicated that the significant pooled ORs were not robust. The subgroup analysis suggested that the carrier of G in rs4804803 was a risk factor for severe dengue under dominant (GG\/GA versus AA: OR = 1.86,95%CI, 1.01\u20133.45), superdominant (GA versus GG\/AA: OR = 1.81,95%CI, 1.02\u20133.21) and a codominant (GA versus AA: OR=1.82,95%CI, 1.02\u20133.26) models in Asians, while it was a protective factor for severe dengue in South-central Americans under recessive (GG versus GA\/AA: OR = 0.27,95%CI, 0.10\u20130.70) and codominant (GG versus AA: OR=0.24,95%CI, 0.09\u20130.64) models. The results from subgroup analysis were robust. Conclusions: Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) promoter-336G\/A (rs4804803) polymorphism is association with severe dengue, and it acts in different directions for Asians and South-central Americans.<\/jats:p>","DOI":"10.3390\/ijerph16081475","type":"journal-article","created":{"date-parts":[[2019,4,25]],"date-time":"2019-04-25T11:19:04Z","timestamp":1556191144000},"page":"1475","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Different Associations between DC-SIGN Promoter-336G\/A (rs4804803) Polymorphism with Severe Dengue in Asians and South-Central Americans: a Meta-Analysis"],"prefix":"10.3390","volume":"16","author":[{"given":"Jiangping","family":"Ren","sequence":"first","affiliation":[{"name":"Zhejiang Provincial Centre for Disease Control and Prevention, Hangzhou 310051, China"},{"name":"Key Laboratory of Vaccine, Prevention and Control of Infectious Disease of Zhejiang Province, Hangzhou 310051, China"},{"name":"Field Epidemiology Training Program of Zhejiang Province, Hangzhou 310051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengting","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Centre for Disease Control and Prevention, Hangzhou 310051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enfu","family":"Chen","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Centre for Disease Control and Prevention, Hangzhou 310051, China"},{"name":"Key Laboratory of Vaccine, Prevention and Control of Infectious Disease of Zhejiang Province, Hangzhou 310051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,4,25]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2018, December 01). Dengue Guidelines for Diagnosis, Treatment, Prevention and Control [EB]. Available online: https:\/\/www.who.int\/neglected_diseases\/resources\/9789241547871\/en\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1016\/S1473-3099(16)00026-8","article-title":"The global burden of dengue: An analysis from the global burden of disease study 2013","volume":"6","author":"Stanaway","year":"2016","journal-title":"Lancet Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/nature12060","article-title":"The global distribution and burden of dengue","volume":"496","author":"Bhatt","year":"2013","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.meegid.2017.11.009","article-title":"Host genetics and dengue fever","volume":"56","author":"Cardoso","year":"2017","journal-title":"Infect. Genet. Evol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s13337-018-0426-8","article-title":"Blood group ab is associated with severe forms of dengue virus infection","volume":"29","author":"Murugananthan","year":"2018","journal-title":"VirusDisease"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Nunes, P.C.G., de Filippis, A.M.B., Lima, M.Q.D.R., Faria, N.R.D.C., de Bruycker-Nogueira, F., Santos, J.B., Heringer, M., Chouin-Carneiro, T., Couto-Lima, D., and de Santis Gon\u00e7alves, B. (2018). 30 years of dengue fatal cases in Brazil: A laboratorial-based investigation of 1047 cases. BMC Infect. Dis., 18.","DOI":"10.1186\/s12879-018-3255-x"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Suppiah, J., Ching, S., Amin-Nordin, S., Mat-Nor, L., Ahmad-Najimudin, N., Low, G.K., Abdul-Wahid, M., Thayan, R., and Chee, H. (2018). Clinical manifestations of dengue in relation to dengue serotype and genotype in Malaysia: A retrospective observational study. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006817"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Huy, N.T., Van Giang, T., Thuy, D.H., Kikuchi, M., Hien, T.T., Zamora, J., and Hirayama, K. (2013). Factors associated with dengue shock syndrome: A systematic review and meta-analysis. PLoS Negl. Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002412"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"670","DOI":"10.4269\/ajtmh.11-0774","article-title":"Determinants of mortality from severe dengue in Brazil: A population-based case-control study","volume":"88","author":"Moraes","year":"2013","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_10","first-page":"334","article-title":"Clinical profile and predictors of severe dengue disease: A study from South India","volume":"9","author":"Agrawal","year":"2018","journal-title":"Casp. J. Intern. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"39872","DOI":"10.1038\/srep39872","article-title":"Diabetes, cardiac disorders and asthma as risk factors for severe organ involvement among adult dengue patients: A matched case-control study","volume":"7","author":"Pang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Thanachartwet, V., Oer-areemitr, N., Chamnanchanunt, S., Sahassananda, D., Jittmittraphap, A., Suwannakudt, P., Desakorn, V., and Wattanathum, A. (2015). Identification of clinical factors associated with severe dengue among Thai adults: A prospective study. BMC Infect. Dis., 15.","DOI":"10.1186\/s12879-015-1150-2"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Machado, C.R., Machado, E.S., Rohloff, R.D., Azevedo, M., Campos, D.P., de Oliveira, R.B., and Brasil, P. (2013). Is pregnancy associated with severe dengue? A review of data from the Rio De Janeiro surveillance information system. PLoS Neglect. Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002217"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Pinto, R.C., Castro, D.B., Albuquerque, B.C., Sampaio, V.D.S., Passos, R.A., Costa, C.F., Sadahiro, M., and Braga, J.U. (2016). Mortality predictors in patients with severe dengue in the state of Amazonas, Brazil. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0161884"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1111\/j.1574-695X.2006.00058.x","article-title":"Dengue and dengue haemorrhagic fever: Implications of host genetics","volume":"47","author":"Chaturvedi","year":"2006","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Carabali, M., Hernandez, L.M., Arauz, M.J., Villar, L.A., and Ridde, V. (2015). Why are people with dengue dying? A scoping review of determinants for dengue mortality. BMC Infect. Dis., 15.","DOI":"10.1186\/s12879-015-1058-x"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1038\/ejhg.2008.4","article-title":"Genetic ancestry and income are associated with dengue hemorrhagic fever in a highly admixed population","volume":"16","author":"Blanton","year":"2008","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"54","DOI":"10.3109\/08830185.2013.834897","article-title":"DC-SIGN, DC-SIGNR and LSECtin: C-type lectins for infection","volume":"33","author":"Zhang","year":"2014","journal-title":"Int. Rev. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Wang, L., Chen, R.F., Liu, J.W., Lee, I.K., Lee, C.P., Kuo, H.C., Huang, S.K., and Yang, K.D. (2011). DC-SIGN (CD209) promoter \u2212336 A\/G polymorphism is associated with dengue hemorrhagic fever and correlated to DC-SIGN expression and immune augmentation. PLoS Negl. Trop. Dis., 5.","DOI":"10.1371\/journal.pntd.0000934"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"28939","DOI":"10.1074\/jbc.M104565200","article-title":"A novel mechanism of carbohydrate recognition by the C-type lectins DC-SIGN and DC-SIGNR","volume":"276","author":"Mitchell","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3939","DOI":"10.1128\/JVI.02484-07","article-title":"Role of dendritic cells in antibody-dependent enhancement of dengue virus infection","volume":"82","author":"Boonnak","year":"2008","journal-title":"J. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1111\/jth.12178","article-title":"Dengue induces platelet activation, mitochondrial dysfunction and cell death through mechanisms that involve DC-SIGN and caspases","volume":"11","author":"Hottz","year":"2013","journal-title":"J. Thromb. Haemost."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1182\/blood-2014-09-598029","article-title":"Dengue virus binding and replication by platelets","volume":"126","author":"Simon","year":"2015","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.actatropica.2017.10.017","article-title":"Associations of DC-SIGN (CD209) promoter-336G\/A polymorphism (rs4804803) with dengue infection: A systematic review and meta-analysis","volume":"177","author":"Pabalan","year":"2018","journal-title":"Acta Trop."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.actatropica.2014.05.021","article-title":"Contrasting associations of polymorphisms in Fc\u03b3RIIa and DC-SIGN with the clinical presentation of dengue infection in a mexican population","volume":"138","author":"Noecker","year":"2014","journal-title":"Acta Trop."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1089\/vim.2013.0119","article-title":"Polymorphism of DC-SIGN (CD209) promoter in association with clinical symptoms of dengue fever","volume":"27","author":"Oliveira","year":"2014","journal-title":"Viral Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.meegid.2013.04.024","article-title":"Association of promoter region polymorphisms of CD209 gene with clinical outcomes of dengue virus infection in Western India","volume":"17","author":"Alagarasu","year":"2013","journal-title":"Infect. Genet. Evol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.meegid.2013.08.017","article-title":"Single nucleotide polymorphisms in candidate genes and dengue severity in children: A case\u2013control, functional and meta-analysis study","volume":"20","author":"Gibson","year":"2013","journal-title":"Infect. Genet. Evol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1038\/ejhg.2010.98","article-title":"Dengue hemorrhagic fever is associated with polymorphisms in JAK1","volume":"18","author":"Silva","year":"2010","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/ng1550","article-title":"A variant in the CD209 promoter is associated with severity of dengue disease","volume":"37","author":"Sakuntabhai","year":"2005","journal-title":"Nat. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"23698","DOI":"10.1074\/jbc.M504337200","article-title":"Dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN)-mediated enhancement of dengue virus infection is independent of DC-SIGN internalization signals","volume":"280","author":"Lozach","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/nature25753","article-title":"Meta-analysis and the science of research synthesis","volume":"555","author":"Gurevitch","year":"2018","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1093\/aje\/kwn359","article-title":"Hardy-weinberg equilibrium testing of biological ascertainment for Mendelian randomization studies","volume":"169","author":"Rodriguez","year":"2009","journal-title":"Am. J. Epidemiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"101","DOI":"10.2149\/tmh.2015-02","article-title":"DC-SIGN (CD209) carbohydrate recognition domain is not polymorphic in dengue virus-infected Indonesian patients","volume":"43","author":"Wibawa","year":"2015","journal-title":"Trop. Med. Health"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/j.humimm.2015.09.026","article-title":"Single nucleotide polymorphisms in immune system genes and their association with clinical symptoms persistence in dengue-infected persons","volume":"76","author":"Dettogni","year":"2015","journal-title":"Hum. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Dang, T.N., Naka, I., Sa-Ngasang, A., Anantapreecha, S., Wichukchinda, N., Sawanpanyalert, P., Patarapotikul, J., Tsuchiya, N., and Ohashi, J. (2016). Association of BAK1 single nucleotide polymorphism with a risk for dengue hemorrhagic fever. BMC Med. Genet., 17.","DOI":"10.1186\/s12881-016-0305-3"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.meegid.2018.04.018","article-title":"Population genetics-informed meta-analysis in seven genes associated with risk to dengue fever disease","volume":"62","author":"Oliveira","year":"2018","journal-title":"Infect. Genet. Evol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Vannberg, F.O., Chapman, S.J., Khor, C.C., Tosh, K., Floyd, S., Jackson-Sillah, D., Crampin, A., Sichali, L., Bah, B., and Gustafson, P. (2008). CD209 genetic polymorphism and tuberculosis disease. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0001388"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/j.humimm.2010.03.006","article-title":"CD209 (DC-SIGN) \u2212336A>G promoter polymorphism and severe acute respiratory syndrome in Hong Kong Chinese","volume":"71","author":"Chan","year":"2010","journal-title":"Hum. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.meegid.2008.12.003","article-title":"CD209 gene polymorphisms in south Indian HIV and HIV-TB patients","volume":"9","author":"Selvaraj","year":"2009","journal-title":"Infect. Genet. Evol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1089\/dna.2015.2819","article-title":"Association of oligoadenylate synthetase gene cluster and DC-SIGN (CD209) gene polymorphisms with clinical symptoms in chikungunya virus infection","volume":"35","author":"Chaaithanya","year":"2016","journal-title":"DNA Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1111\/tra.12469","article-title":"Beyond attachment: Roles of DC-SIGN in dengue virus infection","volume":"18","author":"Liu","year":"2017","journal-title":"Traffic"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Richter, M.K., Da, S.V.J., Torres, P.S., Hoornweg, T.E., van de Pol, D.P., Rodenhuis-Zybert, I.A., Wilschut, J., and Smit, J.M. (2014). Immature dengue virus is infectious in human immature dendritic cells via interaction with the receptor molecule DC-SIGN. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0098785"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1126\/science.aan6836","article-title":"Antibody-dependent enhancement of severe dengue disease in humans","volume":"358","author":"Katzelnick","year":"2017","journal-title":"Science"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1089\/jir.2017.0037","article-title":"Highlights for dengue immunopathogenesis: Antibody-dependent enhancement, cytokine storm, and beyond","volume":"38","author":"Kuczera","year":"2018","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Tomo, S., Mohan, S., Ramachandrappa, V.S., Samadanam, D.M., Suresh, S., Pillai, A.B., Tamilarasu, K., Ramachandran, R., and Rajendiran, S. (2018). Dynamic modulation of DC-SIGN and FcYR2A receptors expression on platelets in dengue. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0206346"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.antiviral.2011.10.017","article-title":"Single nucleotide polymorphism in the promoter region of the CD209 gene is associated with human predisposition to severe forms of tick-borne encephalitis","volume":"93","author":"Barkhash","year":"2012","journal-title":"Antivir. Res."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/16\/8\/1475\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:47:13Z","timestamp":1760186833000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/16\/8\/1475"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,25]]},"references-count":47,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2019,4]]}},"alternative-id":["ijerph16081475"],"URL":"https:\/\/doi.org\/10.3390\/ijerph16081475","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,25]]}}}