TY - JOUR
T1 - Cadherin-related family member 3 gene impacts childhood asthma in Chinese children
AU - Leung, Ting Fan
AU - Tang, Man Fung
AU - Leung, Agnes Sze Yin
AU - Kong, Alice Pik Shan
AU - Liu, Tak Chi
AU - Chan, Renee Wan Yi
AU - Ma, Ronald Ching Wan
AU - Sy, Hing Yee
AU - Chan, Juliana Chung Ngor
AU - Wong, Gary Wing Kin
N1 - Publisher Copyright:
© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
PY - 2020/2/1
Y1 - 2020/2/1
N2 - 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 FEV0.5 (β = −2.411, P =.004) and FEV0.5/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 FEV0.5 among pre-schoolers. Conclusion: CDHR3 is a candidate gene for early-life wheezing, school-age asthma, and lung function in Chinese children.
AB - 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 FEV0.5 (β = −2.411, P =.004) and FEV0.5/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 FEV0.5 among pre-schoolers. Conclusion: CDHR3 is a candidate gene for early-life wheezing, school-age asthma, and lung function in Chinese children.
KW - cadherin-related family member 3
KW - genetic biomarker
KW - incentive spirometry
KW - pre-schoolers
KW - rhinovirus C receptor
KW - wheeze
UR - http://www.scopus.com/inward/record.url?scp=85074839401&partnerID=8YFLogxK
U2 - 10.1111/pai.13138
DO - 10.1111/pai.13138
M3 - Article
C2 - 31610042
AN - SCOPUS:85074839401
SN - 0905-6157
VL - 31
SP - 133
EP - 142
JO - Pediatric Allergy and Immunology
JF - Pediatric Allergy and Immunology
IS - 2
ER -