Complement alternative pathway genetic variation and D engue infection in the T hai population

Summary D engue disease is a mosquito‐borne infection caused by D engue virus. Infection may be asymptomatic or variably manifest as mild D engue fever ( DF ) to the most severe form, D engue haemorrhagic fever ( DHF ). Mechanisms that influence disease severity are not understood. Complement, an integral component of the immune system, is activated during D engue 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, C 3 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 D engue 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 D engue infection severity in the T hai population. However, the minor allele frequencies of the factor B and C 3 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 D engue NS 1 using both recombinant NS 1 and DV 2‐infected culture supernatants. We conclude that the complotype does not influence secondary D engue infection severity in the T hai population.