The pathogenesis of meningococcal infections involves activation of the complement system, proinflammatory and anti-inflammatory mediators, antimicrobial peptides, and apoptosis. We hypothesized that variations in genes encoding these products are involved in the susceptibility to and severity of pediatric meningococcal infections. Polymorphisms in poly (adenosine diphosphate-ribose) polymerase (PARP), serine protease C1 inhibitor (C1INH), IL4, IL10 and IL1B, α-defensin 4, and β-defensin 1 (DEFB1) were analyzed in two independent Caucasian case control cohorts from the United Kingdom and the Netherlands and in a family-based transmission disequilibrium test cohort from the UK. In the UK case control cohort, the DEFB1-44 G/G homozygous genotype was overrepresented in patients with meningococcal disease compared with the G/C and C/C genotypes when combined (odds ratio, 1.57; 95% confidence interval, 1.12-2.20). The transmission disequilibrium test analysis did not confirm this, but did find an association and linkage of the IL4-524 and the C1INH 480 polymorphisms with susceptibility to meningococcal infection. Hematological failure was present more often in UK patients with the DEFB1-44 G/G genotype compared with the C allele carriers (odds ratio, 2.17; 95% confidence interval, 1.22-3.85). Additional studies are necessary to elucidate the conflicting results obtained for the DEFB1, IL4, and C1INH polymorphisms and their role in susceptibility to and severity of meningococcal disease. Copyright

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Keywords genetic variation, immune response, infectious disease, Meningococcal infection, pediatric, transmission disequilibrium test
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Journal Shock (Philadelphia)
Emonts, M, Vermont, C.L, Houwing-Duistermaat, J.J, Haralambous, E, Gaast-De Jongh, C.E, Hazelzet, J.A, … de Groot, R. (2010). Polymorphisms in PARP, IL1B, IL4, IL10, C1INH, DEFB1, and defa4 in meningococcal disease in three populations. Shock (Philadelphia), 34(1), 17–22. doi:10.1097/SHK.0b013e3181ce2c7d