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Childhood asthma is associated with polymorphic markers of PROC on 2q14 in addition to 17q21 locus
Author(s) -
Chan Wa Cheong,
Sy Hing Yee,
Kong Alice P.S.,
Wong Chun K.,
Tse Lai Yin,
Hon Kam Lun,
Chan Juliana C.N.,
Wong Gary W.K.,
Leung Ting Fan
Publication year - 2015
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.12336
Subject(s) - snp , single nucleotide polymorphism , locus (genetics) , genetics , allele , genome wide association study , asthma , biology , genotype , medicine , gene , immunology
Abstract Background Childhood asthma is caused by both genetic and environmental factors. The first genomewide association study ( GWAS ) for asthma revealed putative candidates on nine chromosomal regions in Caucasians, with 17q21 locus being the most widely replicated one. However, there was no replication study for the other loci. This study investigated genetic associations between childhood asthma and autosomal single nucleotide polymorphisms ( SNP s) on eight loci reported in the first GWAS among Hong Kong Chinese. Methods 510 asthmatic children and 510 non‐allergic controls were recruited. 110 tagging SNP s selected based on r 2 ≥ 0.80 and minor allele frequency ≥0.05 for Han Chinese among all SNP s located 50‐kb upstream and downstream of significant autosomal SNP s were genotyped by TaqMan allelic discrimination assays. Transcription factor binding of SNP s was determined by electrophoretic mobility shift assay ( EMSA ). Results Asthma was significantly associated with SNP s on 17q21 and 2q14 loci. Twelve SNP s on 17q21 were associated with asthma, with rs6503527 being the most significant SNP . Five SNP s of protein C gene ( PROC ) on 2q14 were associated with asthma, with rs6755028 being the most significant SNP . Plasma protein C concentrations were higher in asthmatic patients than controls, and five PROC SNP s were associated with plasma protein C concentrations. EMSA showed specific differential binding of rs878461 to nuclear extracts from bronchial epithelial and hepatocarcinoma cell lines. Conclusions Our findings identify PROC on 2q14 as a novel candidate for childhood asthma and replicate the genetic association for 17q21 locus. Rs878461 of PROC may increase asthma susceptibility by altering transcription factor binding.