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Dengue disease is a mosquito-borne infection caused by Dengue virus. Infection may be asymptomatic or variably manifest as mild Dengue fever (DF) to the most severe form, Dengue haemorrhagic fever (DHF). Mechanisms that influence disease severity are not understood. Complement, an integral component of the immune system, is activated during Dengue infection and the degree of activation increases with disease severity. Activation of the complement alternative pathway is influenced by polymorphisms within activation (factor B rs12614/rs641153, C3 rs2230199) and regulatory [complement factor H (CFH) rs800292] proteins, collectively termed a complotype. Here, we tested the hypothesis that the complotype influences disease severity during secondary Dengue infection. In addition to the complotype, we also assessed two other disease-associated CFH polymorphisms (rs1061170, rs3753394) and a structural polymorphism within the CFH protein family. We did not detect any significant association between the examined polymorphisms and Dengue infection severity in the Thai population. However, the minor allele frequencies of the factor B and C3 polymorphisms were less than 10%, so our study was not sufficiently powered to detect an association at these loci. We were also unable to detect a direct interaction between CFH and Dengue NS1 using both recombinant NS1 and DV2-infected culture supernatants. We conclude that the complotype does not influence secondary Dengue infection severity in the Thai population.

Original publication

DOI

10.1111/cei.12184

Type

Journal article

Journal

Clin Exp Immunol

Publication Date

11/2013

Volume

174

Pages

326 - 334

Keywords

Dengue infection, alternative complement pathway, genetic polymorphism, Adolescent, Adult, Cells, Cultured, Child, Child, Preschool, Complement C3, Complement Factor B, Complement Factor H, Complement Pathway, Alternative, Dengue, Dengue Virus, Female, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Polymorphism, Genetic, Thailand, Young Adult