PLoS Genetics (Jul 2011)

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

  • Emiko Noguchi,
  • Hiromi Sakamoto,
  • Tomomitsu Hirota,
  • Kaori Ochiai,
  • Yoshimasa Imoto,
  • Masafumi Sakashita,
  • Fumitake Kurosaka,
  • Akira Akasawa,
  • Shigemi Yoshihara,
  • Noriko Kanno,
  • Yumi Yamada,
  • Naoki Shimojo,
  • Yoichi Kohno,
  • Yoichi Suzuki,
  • Mi-Jin Kang,
  • Ji-Won Kwon,
  • Soo-Jong Hong,
  • Ken Inoue,
  • Yu-Ichi Goto,
  • Fumio Yamashita,
  • Takashi Asada,
  • Hiroshi Hirose,
  • Ikuo Saito,
  • Shigeharu Fujieda,
  • Nobuyuki Hizawa,
  • Toru Sakamoto,
  • Hironori Masuko,
  • Yusuke Nakamura,
  • Ichiro Nomura,
  • Mayumi Tamari,
  • Tadao Arinami,
  • Teruhiko Yoshida,
  • Hirohisa Saito,
  • Kenji Matsumoto

DOI
https://doi.org/10.1371/journal.pgen.1002170
Journal volume & issue
Vol. 7, no. 7
p. e1002170

Abstract

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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.