title: Confirmation of Host Genetic Determinants in the CFH Region and Susceptibility to Meningococcal Disease in a Central European Study Sample.
abstract: BACKGROUND
  Invasive meningococcal disease (IMD) is a leading cause of meningitis and severe sepsis in children and adolescents. Genetic factors are important in determining the susceptibility to and outcome of IMD. Recently, a genome-wide association study from the United Kingdom showed significant associations of single-nucleotide polymorphisms within complement factor H (CFH; rs1065489) and in CFH-related protein 3 (rs426736) with susceptibility of IMD. We report data of a genetic replication study in Central European children.
  
  
  METHODS
  The study was conducted as a retrospective case-reference study involving 248 patients with confirmed diagnosis of IMD from Austria and Germany and 835 healthy reference individuals from a multicenter German birth cohort.
  
  
  RESULTS
  Carriers of the minor alleles of rs1065489 and rs426736 were at lower risk of IMD [allelic odds ratio = 0.60 (0.44-0.82); P = 0.001 and 0.61 (0.45-0.83); P = 0.001]. Also, 2 major haplotypes (GT and TC) derived from the 2 single-nucleotide polymorphisms were significantly associated with IMD (P = 0.001 and P = 0.003, respectively).
  
  
  CONCLUSIONS
  The consistency of the results between the genome-wide association study and our study population strengthens the association of CFH polymorphisms to the susceptibility of IMD. Our results support the conclusion that CFH is a critical determinant in acquiring meningococcal disease.
authors.affiliation: From the *Department of Pediatrics, Academic Teaching Hospital, Feldkirch, Austria; †Department of Pediatrics, Children's Hospital, Linz, Austria; ‡Department of Pediatric Pulmonology and Allergy, University Hospital Regensburg, Regensburg, Germany; §Department of Pediatrics, Pneumonology and Allergology, University Hospital Regensburg, Regensburg, Germany; ¶Department of General Pediatrics, Medical University of Graz, Graz, Austria; ‖Center for Chronic Immunodeficiencies, University Medical Center Freiburg, Freiburg, Germany; **Institute of Social Medicine, Epidemiology and Health Economics, Charité Medical University Berlin; and ††Department of Pediatric Pneumonolgy and Immunology, Charité-Universitaetsmedizin, Berlin, Germany.
authors.forename: Ariane
authors.initials: A
authors.lastname: Biebl
authors.forename: Axel
authors.initials: A
authors.lastname: Muendlein
authors.forename: Elena
authors.initials: E
authors.lastname: Kinz
authors.forename: Heinz
authors.initials: H
authors.lastname: Drexel
authors.forename: Michael
authors.initials: M
authors.lastname: Kabesch
authors.forename: Werner
authors.initials: W
authors.lastname: Zenz
authors.forename: Roland
authors.initials: R
authors.lastname: Elling
authors.forename: Christoph
authors.initials: C
authors.lastname: Müller
authors.forename: Thomas
authors.initials: T
authors.lastname: Keil
authors.forename: Susanne
authors.initials: S
authors.lastname: Lau
authors.forename: Burkhard
authors.initials: B
authors.lastname: Simma
mesh_terms: D001317:Austria / Q000453:epidemiology; D002648:Child; D017242:Complement Factor H / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008589:Meningococcal Infections / Q000453:epidemiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012189:Retrospective Studies
chemical_list: D017242:Complement Factor H