title: Clara cell protein 16 (CC16) gene polymorphism influences the degree of airway responsiveness in asthmatic children.
abstract: BACKGROUND
  Several studies have indicated linkage of chromosome 11q12-13 to asthma and associated traits. Among other candidate genes, the Clara cell protein 16 (CC16) gene maps to this region. CC16 is expressed in the bronchial epithelium and exhibits potent anti-inflammatory properties. A single-nucleotide polymorphism (SNP) in the CC16 gene (A38G) was previously associated with asthma.
  
  
  OBJECTIVE
  We evaluated the role of the CC16 SNP in pediatric asthma and asthma severity in 2 German study populations.
  
  
  METHODS
  The German Multicenter Allergy Study (MAS) cohort (n = 872, 94 asthmatic patients) and 112 allergic asthmatic children recruited in Freiburg, Germany, were included in the present study. Histamine provocations were performed at the age of 7 years in the MAS cohort to determine bronchial hyperreactivity; in the Freiburg study population a standardized exercise-induced decrease in FEV1 was evaluated. For genotyping, melting-curve analysis and restriction enzyme digestion were applied.
  
  
  RESULTS
  No association of the CC16*38A allele with asthma could be observed in either study population. However, in asthmatic subjects (MAS cohort) PC(20)FEV(1) values were significantly lower in individuals homozygous or heterozygous for the CC16*38A allele compared with those in subjects with the CC16*38GG genotype (P <.05 and P <.03, respectively). Similarly, allergic asthmatic patients in the Freiburg cohort showed a significantly greater decrease in FEV1 after exercise when homozygous for the CC16*38A allele compared with that seen in asthmatic patients with the *38AG or *38GG genotype (P <.04 and P =.006, respectively).
  
  
  CONCLUSIONS
  We conclude that the CC16*A38G SNP influences bronchial hyperreactivity and might be a genetic determinant of asthma severity in German children.
authors.affiliation: Department of Pediatric Pneumology and Immunology, Charité-Humboldt University, Berlin, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sengler
authors.forename: Andrea
authors.initials: A
authors.lastname: Heinzmann
authors.forename: Silvija-Pera
authors.initials: SP
authors.lastname: Jerkic
authors.forename: Assia
authors.initials: A
authors.lastname: Haider
authors.forename: Christine
authors.initials: C
authors.lastname: Sommerfeld
authors.forename: Bodo
authors.initials: B
authors.lastname: Niggemann
authors.forename: Susanne
authors.initials: S
authors.lastname: Lau
authors.forename: Johannes
authors.initials: J
authors.lastname: Forster
authors.forename: Antje
authors.initials: A
authors.lastname: Schuster
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kamin
authors.forename: Carl
authors.initials: C
authors.lastname: Bauer
authors.forename: Ingrid
authors.initials: I
authors.lastname: Laing
authors.forename: Peter
authors.initials: P
authors.lastname: LeSouef
authors.forename: Ulrich
authors.initials: U
authors.lastname: Wahn
authors.forename: Klaus
authors.initials: K
authors.lastname: Deichmann
authors.forename: Renate
authors.initials: R
authors.lastname: Nickel
mesh_terms: D000293:Adolescent; D000483:Alleles; D001249:Asthma / Q000503:physiopathology*; D001980:Bronchi / Q000503:physiopathology*; D002648:Child; D015331:Cohort Studies; D015444:Exercise / Q000502:physiology; D005541:Forced Expiratory Volume; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D012720:Severity of Illness Index; D014598:Uteroglobin
chemical_list: D011506:Proteins; C556389:SCGB1A1 protein, human; D014598:Uteroglobin