Molecular cloning of two novel mucin-like genes in the disease-susceptibility locus for diffuse panbronchiolitis.
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.
Hijikata
Minako
M
Department of Respiratory Diseases, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan.
Matsushita
Ikumi
I
Tanaka
Goh
G
Tsuchiya
Tomoko
T
Ito
Hideyuki
H
Tokunaga
Katsushi
K
Ohashi
Jun
J
Homma
Sakae
S
Kobashi
Yoichiro
Y
Taguchi
Yoshio
Y
Azuma
Arata
A
Kudoh
Shoji
S
Keicho
Naoto
N
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
D009077:Mucins