Association of diffuse panbronchiolitis with microsatellite polymorphism of the human interleukin 8 (IL-8) gene

Diffuse panbronchiolitis (DPB) is a distinctive chronic inflammatory lung d isease predominantly found in Asian populations, Although its etiology is u nknown, DPB is considered to be a multifactorial disease of whose susceptib ility is determined by genetic predisposition unique to Asians. We and othe rs have previously reported that the B*5401 allele of the human leukocyte a ntigen (HLA)-B gene or a closely linked gene in the HLA region on 61321.3 i s one of the major genetic factors in susceptibility to this disease. Howev er, the association with B*5401 is not absolute and the contribution of oth er genetic or environmental factors should also be considered. Here, four c andidate genes that are postulated to play a role in the pathophysiology of DPB, namely, RON-kinase, CYP3A4, motilin, and interleukin (IL)-8, were cho sen, and association studies between microsatellite markers at these loci a nd 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; cor rected P [Pc] < 0.05). Although further studies are needed to examine wheth er neutrophil accumulation in the airways of patients with DPB is controlle d 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.