Polymorphism of human major histocompatibility complex-encoded transporter associated with antigen processing (TAP) genes and susceptibility to juvenile rheumatoid arthritis

Abstract

The TAP1 and TAP2 genes encode a peptide transporter supplying peptides for binding to HLA class I molecules. Both genes are located in the class II region of the HLA complex and are polymorphic. Here we report the distribution of TAP alleles in a group of 285 JRA patients (including various subsets), 165 random controls, and 82 DR8-positive controls. We found a pronounced increase of TAP1B and TAP2C/D in patients, compared with controls. The difference was, however, mainly secondary to a strong linkage disequilibrium between these TAP alleles and DR8, which is significantly increased in JRA. When we compared patients and controls after stratification for DR8 the differences decreased, although an increase of TAP1B in DR8-negative patients remained significant. We conclude that a primary association of JRA with given TAP allels cannot explain the HLA class II associations in JRA. However, we cannot exclude the possibility that TAP1B acts as an additive susceptibility factor in JRA.