Childhood asthma is associated with polymorphic markers of PROC on 2q14 in addition to 17q21 locus
Wa Cheong Chan
Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
Search for more papers by this authorHing Yee Sy
Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
Search for more papers by this authorAlice P.-S. Kong
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
Search for more papers by this authorChun K. Wong
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
Search for more papers by this authorLai Yin Tse
Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
Search for more papers by this authorKam Lun Hon
Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
Search for more papers by this authorJuliana C.-N. Chan
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
Search for more papers by this authorGary W.-K. Wong
Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
Search for more papers by this authorCorresponding Author
Ting Fan Leung
Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
Correspondence
Ting Fan Leung, Department of Paediatrics, Prince of Wales Hospital, 6/F, Lui Che Woo Clinical Sciences Building, Shatin, N.T., Hong Kong
Tel.: +852 2632 2981
Fax: +852 2636 0020
E-mail: [email protected]
Search for more papers by this authorWa Cheong Chan
Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
Search for more papers by this authorHing Yee Sy
Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
Search for more papers by this authorAlice P.-S. Kong
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
Search for more papers by this authorChun K. Wong
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
Search for more papers by this authorLai Yin Tse
Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
Search for more papers by this authorKam Lun Hon
Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
Search for more papers by this authorJuliana C.-N. Chan
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
Search for more papers by this authorGary W.-K. Wong
Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
Search for more papers by this authorCorresponding Author
Ting Fan Leung
Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
Correspondence
Ting Fan Leung, Department of Paediatrics, Prince of Wales Hospital, 6/F, Lui Che Woo Clinical Sciences Building, Shatin, N.T., Hong Kong
Tel.: +852 2632 2981
Fax: +852 2636 0020
E-mail: [email protected]
Search for more papers by this authorAbstract
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 (SNPs) 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 SNPs selected based on r2 ≥ 0.80 and minor allele frequency ≥0.05 for Han Chinese among all SNPs located 50-kb upstream and downstream of significant autosomal SNPs were genotyped by TaqMan allelic discrimination assays. Transcription factor binding of SNPs was determined by electrophoretic mobility shift assay (EMSA).
Results
Asthma was significantly associated with SNPs on 17q21 and 2q14 loci. Twelve SNPs on 17q21 were associated with asthma, with rs6503527 being the most significant SNP. Five SNPs 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 SNPs 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.
Supporting Information
| Filename | Description |
|---|---|
| pai12336-sup-0001-TabS1-S7-FigS1.docWord document, 682.5 KB | Table S1. Summary of genotyping efficiency for SNPs on all chromosomal regions in this study. Table S2. Genetic associations between asthma and SNPs on chromosome 2q14 locus. Table S3. Association between asthma diagnosis and SNPs on chromosome 17q12-21 locus. Table S4. Minor allele frequencies of our genotyped SNPs among different Asian populations and p-values of their genetic associations with asthma diagnosis in our Chinese children. Table S5. GMDR analysis for SNP-SNP interactions on 2q14 and 17q21 loci. Table S6. Transcription factors predicted binding to rs878461 and rs1799810. Table S7. Comparison of SNPs on chromosome 17q21 locus with published data. Figure S1. EMSA reactions for (a) rs878461 and (b) rs1799810 on 2q14. (a) Allele-specific protein-DNA binding at PROC involving C and T allele of rs878461 was shown using nuclear extracts from HepG2 cell line. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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