title: Molecular cloning of two novel mucin-like genes in the disease-susceptibility locus for diffuse panbronchiolitis.
abstract: Diffuse panbronchiolitis (DPB) is a rare complex genetic disease affecting East Asians and is strongly associated with the class I human leukocyte antigens (HLA)-B54 in Japanese and HLA-A11 in Koreans. We recently showed that an HLA-associated major susceptibility gene for DPB 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. We cloned two novel mucin-like genes designated panbronchiolitis related mucin-like 1 and 2 (PBMUCL1 and PBMUCL2) in the candidate region, which form a mucin-like gene cluster together with two adjacent genes, MUC21 and DPCR1. PBMUCL1 gene expression was remarkably upregulated by polyinosine-polycytidylic acid [poly(I:C)] stimulation in normal human bronchial epithelial cells redifferentiated at the air-liquid interface. We found genetic polymorphisms in PBMUCL1 gene which were associated with DPB: the A-allele of the PBMUCL1 intron 2 single nucleotide polymorphism (SNP) was positively associated and variable numbers of tandem repeats (VNTR) polymorphism in exon 3 (1,890-base pair deletion) was negatively associated. Despite a strong association with HLA-B in the Japanese, the mucin-like gene PBMUCL1 is also one of the candidate genes of DPB susceptibility.
authors.affiliation: Department of Respiratory Diseases, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan.
authors.forename: Minako
authors.initials: M
authors.lastname: Hijikata
authors.forename: Ikumi
authors.initials: I
authors.lastname: Matsushita
authors.forename: Goh
authors.initials: G
authors.lastname: Tanaka
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tsuchiya
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ito
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.forename: Jun
authors.initials: J
authors.lastname: Ohashi
authors.forename: Sakae
authors.initials: S
authors.lastname: Homma
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Kobashi
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Taguchi
authors.forename: Arata
authors.initials: A
authors.lastname: Azuma
authors.forename: Shoji
authors.initials: S
authors.lastname: Kudoh
authors.forename: Naoto
authors.initials: N
authors.lastname: Keicho
mesh_terms: D000595:Amino Acid Sequence; D001988:Bronchiolitis / Q000235:genetics; D002478:Cells, Cultured; D003001:Cloning, Molecular; D005805:Genes, MHC Class I; D020022:Genetic Predisposition to Disease; D006192:Haemophilus Infections / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009077:Mucins / Q000235:genetics
chemical_list: D009077:Mucins