POLYMORPHISMS IN PARP, IL1B, IL4, IL10, C1INH, DEFB1, AND DEFA4 IN MENINGOCOCCAL DISEASE IN THREE POPULATIONS

被引：11
作者：
Emonts, Marieke [1 ]
Vermont, Clementien L. [1 ]
Houwing-Duistermaat, Jeanine J. [2 ]
Haralambous, Elene [3 ]
Gaast-de Jongh, Christa E. [4 ]
Hazelzet, Jan A. [1 ]
Faust, Saul N. [5 ,6 ]
Betts, Helen [3 ]
Hermans, Peter W. M. [4 ]
Levin, Michael [3 ]
de Groot, Ronald [4 ]
机构：
[1] Erasmus MC Sophia Childrens Hosp, Dept Pediat, Univ Med Ctr, Rotterdam, Netherlands
[2] Leiden Univ Med Ctr, Dept Med Stat, Leiden, Netherlands
[3] Univ London Imperial Coll Sci Technol & Med, Dept Pediat, London, England
[4] Radboud Univ Nijmegen Med Ctr, Dept Pediat, Nijmegen, Netherlands
[5] Univ Southampton, Div Infect Inflammat & Immun, Southampton, Hants, England
[6] Univ Southampton, Wellcome Trust Clin Res Facil, Southampton, Hants, England
来源：
SHOCK | 2010年 / 34卷 / 01期
关键词：
Meningococcal infection; immune response; genetic variation; pediatric; infectious disease; transmission disequilibrium test; SEPTIC SHOCK; C1; INHIBITOR; GENE; ASSOCIATION; CHILDREN; SUSCEPTIBILITY; INTERLEUKIN-4; GENOTYPE; RECEPTOR; SEPSIS;
D O I：
10.1097/SHK.0b013e3181ce2c7d
中图分类号：
R4 [临床医学];
学科分类号：
1002 ; 100602 ;
摘要：
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, alpha-defensin 4, and beta-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.
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页码：17 / 22
页数：6
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