Abstract
Background: About 20-40% of preschool children experience wheezing. One in three wheezers will have persistent symptoms after the age of six and develop asthma. It is unknown which gene variants contribute to wheezing.
Aim: To explore the relation between asthma associated single nucleotide polymorphisms (SNPs) and preschool recurrent wheezers.
Methods: We selected 202 recurrent wheezers (ISAAC questionnaire ≥2 wheezing episodes) and 50 controls aged 2-4 years. Saliva and buccal swaps were used for DNA extraction. Chi square tests were performed on 23 SNPs in 15 genes. Results were expressed in unadjusted odds ratio (OR) with 95% confidence interval. Multiple testing was corrected by the Benjamini and Hochberg False Discovery Rate.
Results: In total 134 boys and 116 girls participated with an average age of 3.3 years. All SNPs had a high call rate (94.0-99.2%). The frequencies of a genetic variant in ADAM33 (rs511898) differed statistically significantly between cases and controls leading to OR=2.4 (1.2-4.9) for CT genotype and OR=1.0 (0.4-2.5) for TT genotype compared to CC genotype (p=0.03). The frequencies of a genetic variant in ORMLD3 (rs7216389) differed statistically significant between cases and controls leading to OR=3.7 (1.7-8.2) for CT genotype and OR=2.7 (1.2-6.3) for TT genotype compared to CC genotype (p<0.01). Neither remained statistically significant after multiple testing correction (rs511898 p=0.36, rs7216389 p=0.07).
Conclusions: We observed some evidence for the association of the ORMDL3 SNP rs7216389 and recurrent wheeze. The T-allele was more frequent in recurrent wheezers, which is consistent with previous studies in asthma.
- © 2011 ERS