Gender-dependent association between exhaled nitric oxide and the CC16 38AA genotype in young school children

Studies that investigated the association between the CC16 A38G polymorphism and the risk of asthma yielded conflicting results. The aim of this study among schoolchildren was to assess the relationships of CC16 A38G polymorphism with aeroallergen sensitization and fractional exhaled nitric oxide (FeNO), two outcomes predicting asthma later in life.

The study included 139 children (72 boys), median age of 7.7. Information on each child's health, lifestyle, and environment was collected through a questionnaire completed by their parents. CC16 genotypes were determined using urinary DNA. We measured FeNO, the CC16 protein in urine and nasal lavage fluid and aeroallergen-specific immunoglobulin E in nasal mucosa fluid.

Children with the homozygous mutant CC16 38AA genotype had higher odds of increased FeNO (>30 ppb) compared with their peers with the wild-type genotype 38GG (OR, 9.85; 95% CI, 2.09-46.4; P = .004). This association was female gender specific (P = .002) not being observed in boys (P = .40). It was also independent of allergic sensitization, which yet emerged as the strongest predictor of FeNO along with the use of bleach for house cleaning. Children with the CC16 38AA genotype had lower covariates-adjusted urinary CC16 levels than those with 38GG (median, μg/L, 1.17 vs 2.08, P = .02).

Our study suggests that the CC16 38AA allele promotes airway inflammation as measured by FeNO through a gender-dependent association. Deficient levels of CC16 in the deep lung, measured noninvasively in urine, as a possible proxy for serum CC16, might underlie this promoting effect.