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Cadherin‐related family member 3 gene impacts childhood asthma in Chinese children
Author(s) -
Leung Ting Fan,
Tang Man Fung,
Leung Agnes Sze Yin,
Kong Alice Pik Shan,
Liu Tak Chi,
Chan Renee Wan Yi,
Ma Ronald Ching Wan,
Sy Hing Yee,
Chan Juliana Chung Ngor,
Wong Gary Wing Kin
Publication year - 2020
Publication title -
pediatric allergy and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.269
H-Index - 89
eISSN - 1399-3038
pISSN - 0905-6157
DOI - 10.1111/pai.13138
Subject(s) - medicine , wheeze , asthma , odds ratio , minor allele frequency , confidence interval , multifactor dimensionality reduction , single nucleotide polymorphism , cohort , haplotype , pediatrics , demography , allele , genetics , genotype , gene , biology , sociology
Abstract Background A missense variant (rs6967330) of the gene encoding cadherin‐related family member 3 ( CDHR3 ) was associated with recurrent severe exacerbations in pre‐schoolers. However, there were limited data on its relationship with pre‐school lung function and school‐age asthma. This study replicated the association between polymorphic markers at the region of CDHR3 around rs6967330 and wheezing phenotypes in two independent cohorts of Chinese children. Methods Ten tagging SNPs located 10 kb around rs6967330 were selected by HaploView 5.0 based on 1000 Genomes database for Southern Han Chinese. Their associations with wheezing and lung function were examined in 1341 Chinese pre‐school children, while those for asthma phenotypes were examined in an independent group of 2079 school‐age children. Genotypic and haplotypic associations were analyzed by multivariate regression, and generalized multifactor dimensionality reduction was used to examine epistatic interactions for wheezing traits. Results The mean (SD) age of pre‐school cohort was 4.7 (1.0) years. Rs6967330 was associated with current wheeze (odds ratio [OR] 1.63, 95% confidence interval [CI] 1.09‐2.43) and its severity (OR 1.64, 95% CI 1.10‐2.44) among pre‐school children. This SNP was also associated with school‐age asthma (OR 1.32, 95% CI 1.04‐1.69). The minor allele of rs408223 was associated with lower FEV 0.5 ( β = −2.411, P = .004) and FEV 0.5 /FVC ( β = −1.292, P = .015). Lower spirometric indices were also associated with minor allele of rs140154310. GAC haplotype from rs4730125, rs6967330, and rs408223 was associated with pre‐school current wheeze and school‐age asthma. Epistatic interaction was found between unrelated CDHR3 SNPs for FEV 0.5 among pre‐schoolers. Conclusion CDHR3 is a candidate gene for early‐life wheezing, school‐age asthma, and lung function in Chinese children.