Fine localization of a major disease-susceptibility locus for diffuse panbronchiolitis

Naoto Keicho, Jun Ohashi, Gen Tamiya, Koichiro Nakata, Yoshio Taguchi, Arata Azuma, Nobuya Ohishi, Mitsuru Emi, Myoung Hee Park, Hidetoshi Inoko, Katsushi Tokunaga, Shoji Kudoh

Research output: Contribution to journalArticlepeer-review

60 Citations (Scopus)

Abstract

Diffuse panbronchiolitis affecting East Asians is strongly associated with the class I human leukocyte antigen (HLA) alleles. Recent observations suggest that a major disease-susceptibility gene may be located between the HLA-B and HLA-A loci in the class I region of the major histocompatibility complex on chromosome 6. To test this possibility, we analyzed 14 polymorphic markers in 92 Japanese patients and 93 healthy controls. Of these, seven marker alleles, including HLA-B54 and HLA-A11, were significantly associated with the disease. Maximum-likelihood haplotype analysis and subsequent direct determination of individual haplotypes identified a group of disease- associated haplotypes, one of which contained all seven disease-associated marker alleles. Another haplotype, containing HLA-B*5504, was also associated with the disease. All these haplotypes seem to have diverged from a common ancestral haplotype in East Asians and share a specific segment containing three consecutive markers between the S and TFIIH loci in the class I region. Furthermore, one of the markers within the candidate region showed the highest delta value, indicating the strongest association. Of 20 Korean patients with diffuse panbronchiolitis, 17 also shared the combination of the disease-associated marker alleles within the candidate region. These results indicate that an HLA-associated major susceptibility gene for diffuse panbronchiolitis is probably located within the 200 kb in the class I region 300 kb telomeric of the HLA-B locus on the chromosome 6p21.3.

Original languageEnglish
Pages (from-to)501-507
Number of pages7
JournalAmerican Journal of Human Genetics
Volume66
Issue number2
DOIs
Publication statusPublished - 2000

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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