Contribution of TAP genes to genetic predisposition for diffuse panbronchiolitis

Diffuse panbronchiolitis is a chronic obstructive pulmonary disease found i n Asian populations. Although diffuse panbronchiolitis is considered to be a multifactorial disease of unknown etiology; the disease susceptibility ap pears to be determined by a genetic predisposition unique to Asians An earl ier study showed that human leukocyte antigen (HLA)-B54 predominantly found in East Asians was strongly associated with the disease. A possible interp retation of this association is that the class I molecule or class I antige n presenting system is directly involved in its pathogenesis. Recent observ ations in which impaired expression of class I molecules causes a syndrome resembling diffuse panbronchiolitis further prompted us to test this possib ility. Genes of the molecules implicated in the class I pathway, TAP1, TAP2 and LMP2, which are located in the HLA region of the sixth chromosome were analyzed in 76 patients with diffuse panbronchiolitis and 120 normal contr ols. The combination of A-665 and Gln-687 in exon 11 of the TAP2 gene was a ssociated with the disease (P=0.0028, P-c<0.05). Although this positive ass ociation might be partly explained by linkage disequilibrium with HLA-B*540 1, this TAP2 variation was associated with the disease even in the B*5401-n egative subgroup. On the other hand the His-60 substitution within the LMP2 gene exhibited a negative association with the disease. This negative asso ciation, however could be explained by a strong linkage disequilibrium with HLA-B44 which showed a negative association with the disease in the previo us study These results support the notion that diffuse panbronchiolitis is influenced by genetic factors in the HLA region. Besides the class I gene i tself, genes relevant to the class I antigen presenting system might contri bute to its genetic predisposition.