Transporter associated with antigen processing (TAP) 1 gene polymorphisms in patients with hypersensitivity pneumonitis

Hypersensitivity pneumonitis (HP) is a lung inflammatory disease caused by the inhalation of a variety of antigens. Previous studies support the role of the major histocompatibility complex (MHC) class It genes in the susceptibility to develop HP. However, the putative role of other MHC loci has not been elucidated. Transporters associated with antigen processing (TAP) genes are located within the MHC class 11 region and play an important role transporting peptides across the endoplasmic reticulum membrane for MHC class I molecules assembly. The distribution of single nucleotide polymorphisms (SNPs) in TAP1 genes was analyzed in 73 hypersensitivity pneumonitis (HP) patients and 58 normal subjects. We found a significant association of the allele Gly-637 (GGC) (p = 0.00004, OR = 27.30, CI = 3.87-548.04) and the genotypes Asp-637/Gly-637 (p = 0.01, OR = 16.0, CI = 2.19-631.21), Pro-661/Pro-661 (p = 0.006, OR = 11.30, CI = 2.28-75.77) with HP. A significant decrease in the frequency of the allele Pro-661 (CCA) (p = 0.008, OR = 0.06, CI = 0-0.45), the genotype Asp-637/Asp-637 (p = 0.01, OR = 0.17, 95% CI = 0.05-0.58) and the haplotype [Val-333 (GTC), Val-458 (GTG), Gly-637 (GGC), Pro-661 (CCA)] was detected in HP patients compared with controls (p = 0.002, OR = 0.07, CI = 0.0-0.57). These findings suggest that TAPI gene polymorphisms are related to HP risk, and highlight the importance of the MHC in the development of this disease. (C) 2008 Elsevier Inc. All rights reserved.