Association of diffuse panbronchiolitis with microsatellite polymorphism of the human interleukin 8 (IL-8) gene.
Diffuse panbronchiolitis (DPB) is a distinctive chronic inflammatory lung disease predominantly found in Asian populations. Although its etiology is unknown, DPB is considered to be a multifactorial disease of whose susceptibility is determined by genetic predisposition unique to Asians. We and others have previously reported that the B*5401 allele of the human leukocyte antigen (HLA)-B gene or a closely linked gene in the HLA region on 6p21.3 is one of the major genetic factors in susceptibility to this disease. However, the association with B*5401 is not absolute and the contribution of other genetic or environmental factors should also be considered. Here, four candidate genes that are postulated to play a role in the pathophysiology of DPB, namely, RON-kinase, CYP3A4, motilin, and interleukin (IL)-8, were chosen, and association studies between microsatellite markers at these loci and DPB were conducted. We demonstrated the presence of a specific allele at the IL-8 locus was associated with the disease (c2 = 9.13; P = 0.0025; corrected P [Pc] < 0.05). Although further studies are needed to examine whether neutrophil accumulation in the airways of patients with DPB is controlled by a possible genetic variation of IL-8 or other chemokine genes located in the region 4q12-q13, our data suggest that genes other than those of the HLA system may also contribute to a genetic predisposition to DPB.
D044466:Asian People / Q000235:genetics*; D001988:Bronchiolitis / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005787:Gene Frequency; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D007564:Japan; D018895:Microsatellite Repeats; D006899:Mixed Function Oxygenases / Q000235:genetics; D009037:Motilin / Q000235:genetics; D020412:Multifactorial Inheritance; D011110:Polymorphism, Genetic; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics