Clara cell protein 16 (CC16) gene polymorphism influences the degree of airway responsiveness in asthmatic children.
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.
Sengler
Claudia
C
Department of Pediatric Pneumology and Immunology, Charité-Humboldt University, Berlin, Germany.
Heinzmann
Andrea
A
Jerkic
Silvija-Pera
SP
Haider
Assia
A
Sommerfeld
Christine
C
Niggemann
Bodo
B
Lau
Susanne
S
Forster
Johannes
J
Schuster
Antje
A
Kamin
Wolfgang
W
Bauer
Carl
C
Laing
Ingrid
I
LeSouef
Peter
P
Wahn
Ulrich
U
Deichmann
Klaus
K
Nickel
Renate
R
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
D011506:Proteins; C556389:SCGB1A1 protein, human; D014598:Uteroglobin