title: Childhood asthma is associated with polymorphic markers of PROC on 2q14 in addition to 17q21 locus.
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 (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 r(2 ) ≥ 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.
authors: Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
authors: Wa Cheong
authors: WC
authors: Chan
authors: Hing Yee
authors: HY
authors: Sy
authors: Alice P-S
authors: AP
authors: Kong
authors: Chun K
authors: CK
authors: Wong
authors: Lai Yin
authors: LY
authors: Tse
authors: Kam Lun
authors: KL
authors: Hon
authors: Juliana C-N
authors: JC
authors: Chan
authors: Gary W-K
authors: GW
authors: Wong
authors: Ting Fan
authors: TF
authors: Leung
mesh_terms: D000293:Adolescent; D044466:Asian People / Q000235:genetics; D001249:Asthma / Q000235:genetics*; D002648:Child; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011486:Protein C / Q000235:genetics*
chemical_list: D011486:Protein C
keywords: childhood asthma; chromosome 2q14; genetics; protein C; transcription factor binding