Genome-wide association study identifies HLA-DP as a susceptibility gene for pediatric asthma in Asian populations

PLoS Genet. 2011 Jul;7(7):e1002170. doi: 10.1371/journal.pgen.1002170. Epub 2011 Jul 21.

Abstract

Asthma is a complex phenotype influenced by genetic and environmental factors. We conducted a genome-wide association study (GWAS) with 938 Japanese pediatric asthma patients and 2,376 controls. Single-nucleotide polymorphisms (SNPs) showing strong associations (P<1×10(-8)) in GWAS were further genotyped in an independent Japanese samples (818 cases and 1,032 controls) and in Korean samples (835 cases and 421 controls). SNP rs987870, located between HLA-DPA1 and HLA-DPB1, was consistently associated with pediatric asthma in 3 independent populations (P(combined) = 2.3×10(-10), odds ratio [OR] = 1.40). HLA-DP allele analysis showed that DPA1*0201 and DPB1*0901, which were in strong linkage disequilibrium, were strongly associated with pediatric asthma (DPA1*0201: P = 5.5×10(-10), OR = 1.52, and DPB1*0901: P = 2.0×10(-7), OR = 1.49). Our findings show that genetic variants in the HLA-DP locus are associated with the risk of pediatric asthma in Asian populations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Alleles
  • Asian People / genetics*
  • Asthma / genetics*
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study
  • HLA-DP Antigens / genetics*
  • HLA-DP alpha-Chains / genetics
  • HLA-DP beta-Chains / genetics
  • Haplotypes
  • Humans
  • Male
  • Polymorphism, Single Nucleotide / genetics

Substances

  • HLA-DP Antigens
  • HLA-DP alpha-Chains
  • HLA-DP beta-Chains
  • HLA-DPA1 antigen
  • HLA-DPB1 antigen