Asthma diagnosis was associated with single-nucleotide polymorphisms of the gene encoding human rhinovirus-C receptor in children
Refereed conference paper presented and published in conference proceedings

摘要Background and Aims: Asthma is a common obstructive lung disease in children. Rs6967330 of CDHR3, being the gene encoding human rhinovirus-C (HRV-C) receptor, was reported to be a risk factor for severe asthma exacerbations in Danish preschoolers. Recent data suggested that the mutant of this single-nucleotide polymorphism (SNP) increased bronchial epithelial susceptibility to HRV-C infection, but the relevance of CDHR3 for asthma diagnosis remains unclear. This study investigated the association between CDHR3 and childhood asthma diagnosis and subphenotypes.

Methods: Ten tagging SNPs located within 5-kb both upstream and downstream from rs6967330 were selected by HaploView 5.0 based on 1000 Genomes database searched at pairwise r2 ≥0.8 for linkage disequilibrium (LD) for all SNPs with minor allele frequencies (MAFs) ≥0.01 in Southern Han Chinese (CHS). These tagging SNPs were genotyped by TaqMan assays on QuantStudio 12K Flex real-time PCR system. Genetic associations between these SNPs and categorical and quantitative variables were analysed by logistic and linear regression, respectively, fitted for recessive and co-dominant models.

Results: 903 Chinese children with asthma and 1205 non-allergic controls were recruited, with their mean (SD) age in years being 11.0 (4.1) and 13.6 (4.5). Atopy, defined as having at least one positive skin prick test or aeroallergen-specific immunoglobulin E, occurred in 75.3% of patients and 37.9% of controls (p<0.0001). The overall genotyping efficiency was ≥95%. MAFs of tested SNPs were comparable to those published for CHS, except rs448025 and rs543085868 which were monomorphic. Asthma diagnosis was significantly associated with rs6967330 under addictive model (odds ratio [OR] 1.34 and 95% confidence interval [CI] 1.00-1.80; p=0.049) and dominant model (OR 1.40 and 95% CI 1.03-1.90; p=0.032). This SNP, however, was not associated with atopy or spirometric indices. None of the other SNPs was associated with asthma diagnosis or subphenotypes.

Conclusions: Rs6967330 of CDHR3 is associated with asthma susceptibility in Hong Kong Chinese children, but none of the SNPs is associated with patients’ lung function. Whereas these results may reflect the importance of HRV-C infection in modulating asthma susceptibility, prospective studies with larger sample size are needed to confirm this genetic association.
著者YuPing Song, Man-Fung Tang, Agnes Sze-Yin Leung, Renee Wan-Yi Chan, Gary Wing-kin Wong, Ting-Fan Leung
會議名稱13th Congress of Asian Society for Pediatric Research
會議地點Hong Kong
會議論文集題名13th Congress of Asian Society for Pediatric Research

上次更新時間 2018-11-05 於 14:38