Chromosome 17 variants specific to childhood asthma and wheezing
medwireNews: Genetic variations at the 17q21 locus on chromosome 17 are specific to childhood asthma and certain wheezing phenotypes and not to more general phenotypes such as atopy or lung function, according to the results of an international study.
Explaining the potential implications of their findings, Raquel Granell (University of Bristol, UK) and colleagues say: "Elucidation of causal mechanisms has the potential to facilitate disease prediction in children with wheezing in the preschool years, to contribute to the separation of discrete phenotypes of childhood asthma, and to identify risk factors that might be targets for primary or secondary disease prevention."
The researchers assessed data on 7045 children from the Avon Longitudinal Study of Parents and Children birth cohort, determining the presence of 244 independent single nucleotide polymorphisms (SNPs) and 13 previously identified asthma SNPs between 34 Mb and 36 Mb on chromosome 17.
Associations were examined between the SNPs and early wheezing phenotypes, doctor-diagnosed asthma and atopy at 7.5 years, and bronchial hyperresponsiveness (BHR) and lung function at 8.5 years.
The team notes in the Journal of Allergy and Clinical Immunology that 19.7% of children had asthma, 46.7% had an asthmatic or allergic mother, 22.3% were exposed to maternal smoking during pregnancy, and 20.1% were atopic.
Regarding wheezing phenotypes, 68.4% of children had never/infrequent wheezing, 10.2% had transient early wheezing, 7.5% had prolonged early wheezing, 2.3% had intermediate onset, 4.8% late onset, and 7.0% had persistent wheezing.
The strongest associations with doctor-diagnosed asthma were seen with the asthma-related SNPs rs9303277 near IKZF3 and rs2290400 near GSDML, both at odds ratios (ORs) of 1.30. For BHR, the strongest associations were with rs1042658 near CSF3 and with rs3859192 near GSDM1, at ORs of 1.20 and 1.19, respectively.
For wheezing phenotypes, SNPs near the IKZF3, ZPBP2, GSDML, ORMDL3, and GSDM1 genes were associated with intermediate-onset and persistent wheezing, at relative risk ratios (RRRs) ranging from 1.46 to 1.60. The strongest associations observed were between persistent wheezing and rs8076131 near ORMDL3, rs2305480 near GSDML, and rs9303277 near IKZF3, at RRRs of 1.60, 1.60, and 1.57, respectively. Associations with other wheezing phenotypes were weaker.
The strongest associations with gene specific expression levels were for rs9303277 (in IKZF3) with ORMDL3, IKZF3, and GSDML expression, rs11557467 (in ZPBP2) with ORMDL3, IKZF3, and GSDML expression, rs2290400 (in GSDML) with ORMDL3, IKZF3, and GSDML expression, and rs4378650 (in ORMDL3) with ORMDL3, IKZF3, and GSDML expression.
By Liam Davenport, medwireNews Reporter