title: Transporter associated with antigen processing (TAP) 1 gene polymorphisms in patients with hypersensitivity pneumonitis.
abstract: 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 II 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 II 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 TAP1 gene polymorphisms are related to HP risk, and highlight the importance of the MHC in the development of this disease.
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias, Tlalpan 4502, Col. Sección XVI, 14080, Mexico City, Mexico.
authors.forename: Arnoldo
authors.initials: A
authors.lastname: Aquino-Galvez
authors.forename: Angel
authors.initials: A
authors.lastname: Camarena
authors.forename: Martha
authors.initials: M
authors.lastname: Montaño
authors.forename: Armida
authors.initials: A
authors.lastname: Juarez
authors.forename: Ana C
authors.initials: AC
authors.lastname: Zamora
authors.forename: Georgina
authors.initials: G
authors.lastname: González-Avila
authors.forename: Marco
authors.initials: M
authors.lastname: Checa
authors.forename: Gabriel
authors.initials: G
authors.lastname: Sandoval-López
authors.forename: Gilberto
authors.initials: G
authors.lastname: Vargas-Alarcon
authors.forename: Julio
authors.initials: J
authors.lastname: Granados
authors.forename: Annie
authors.initials: A
authors.lastname: Pardo
authors.forename: Joaquín
authors.initials: J
authors.lastname: Zúñiga
authors.forename: Moisés
authors.initials: M
authors.lastname: Selman
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000542:Alveolitis, Extrinsic Allergic / Q000235:genetics* / Q000473:pathology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; C073119:TAP1 protein, human