title: Genetic susceptibility to multicase hypersensitivity pneumonitis is associated with the TNF-238 GG genotype of the promoter region and HLA-DRB1*04 bearing HLA haplotypes.
abstract: Hypersensitivity Pneumonitis (HP) is a lung inflammatory disorder caused by inhalation of organic particles by a susceptible host. Since only a small proportion of individuals exposed to HP-related antigens develop the disease, a genetic predisposition is largely suspected. However, studies regarding genetic susceptibility in this disease are scanty. We have previously found evidence supporting increased risk associated to the major histocompatibility complex (MHC) in sporadic HP. In the present study, we conducted a family-based research that includes nine multicase families with at least two related HP patients (RHP). We evaluated 19 RHP individuals, 25 additional healthy first-degree relatives (REA) and 246 healthy unrelated individuals (HUI). HLA class II typing (DRB1/3/4/5, DQA1, DQB1, DPA1, DPB1, DMA and DMB), and -863, -308 and -238 polymorphisms in the promoter region of TNF-α were performed by PCR based methods. We identified an increased frequency of HLA-DRB1*04:07, DRB1*04:05, DRB1*11:01 and DRB1*13:01 alleles in RHP individuals compared to healthy controls (p < 0.05). A significant higher frequency of DRB1*04:07-DQB1*03:02, DRB1*04:05-DQB1*03:02, and DRB1*04:03-DQB1*03:02 haplotypes was also detected in the group of patients. Likewise, TNF-238 GG genotype was more frequent in the RHP group as compared to REA (p = 0.01, OR = 7.2). Finally, the combination of HLA-DRB1*04 alleles and TNF-238 GG was significantly increased in the RHP group (p = 0.01, OR = 6.93). These findings indicate that genes located within the MHC region confer susceptibility to familial HP in Mexicans.
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Tlalpan, 14080 Mexico City, Mexico.
authors.forename: Ramcés
authors.initials: R
authors.lastname: Falfán-Valencia
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Tlalpan, 14080 Mexico City, Mexico.
authors.forename: Angel
authors.initials: A
authors.lastname: Camarena
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Tlalpan, 14080 Mexico City, Mexico.
authors.forename: César Landa
authors.initials: CL
authors.lastname: Pineda
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Tlalpan, 14080 Mexico City, Mexico.
authors.forename: Martha
authors.initials: M
authors.lastname: Montaño
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Tlalpan, 14080 Mexico City, Mexico.
authors.forename: Armida
authors.initials: A
authors.lastname: Juárez
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Tlalpan, 14080 Mexico City, Mexico.
authors.forename: Ivette
authors.initials: I
authors.lastname: Buendía-Roldán
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Tlalpan, 14080 Mexico City, Mexico.
authors.forename: Gloria
authors.initials: G
authors.lastname: Pérez-Rubio
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Tlalpan, 14080 Mexico City, Mexico.
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Reséndiz-Hernández
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Tlalpan, 14080 Mexico City, Mexico.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Páramo
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Tlalpan, 14080 Mexico City, Mexico.
authors.forename: Anita
authors.initials: A
authors.lastname: Vega
authors.affiliation: Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Tlalpan, 14080 Mexico City, Mexico.
authors.forename: Julio
authors.initials: J
authors.lastname: Granados
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Tlalpan, 14080 Mexico City, Mexico. Electronic address: joazu@yahoo.com.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Zúñiga
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Tlalpan, 14080 Mexico City, Mexico. Electronic address: mselmanl@yahoo.com.mx.
authors.forename: Moisés
authors.initials: M
authors.lastname: Selman
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000542:Alveolitis, Extrinsic Allergic / Q000175:diagnosis / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D010290:Parents; D011110:Polymorphism, Genetic; D000091402:Prohibitins; D035781:Siblings; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D015415:Biomarkers; D059811:HLA-DRB1 Chains; C527195:HLA-DRB1*04 antigen; C000717331:PHB2 protein, human; D000091402:Prohibitins; D014409:Tumor Necrosis Factor-alpha
keywords: Familial HP; Genetic susceptibility; HLA polymorphisms; Hypersensitivity pneumonitis; MHC genes; TNF promoter polymorphisms