sRAGE levels are decreased in plasma and sputum of COPD secondary to biomass-burning smoke and tobacco smoking: Differences according to the rs3134940 AGER variant
Ingrid Fricke-Galindo,
Salvador García-Carmona,
Jesús Alanis-Ponce,
Gloria Pérez-Rubio,
Alejandra Ramírez-Venegas,
Francisco Montiel-Lopez,
Robinson Robles-Hernández,
Rafael de Jesús Hernández-Zenteno,
Daniela Valencia-Pérez Rea,
Brandon Bautista-Becerril,
María Elena Ramírez-Díaz,
Filiberto Cruz-Vicente,
María de Lourdes Martínez-Gómez,
Raúl Sansores,
Ramcés Falfán-Valencia
Affiliations
Ingrid Fricke-Galindo
HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, 14080, Mexico
Salvador García-Carmona
HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, 14080, Mexico
Jesús Alanis-Ponce
HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, 14080, Mexico
Gloria Pérez-Rubio
HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, 14080, Mexico
Alejandra Ramírez-Venegas
Tobacco Smoking and COPD Research Department, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, 14080, Mexico
Francisco Montiel-Lopez
Tobacco Smoking and COPD Research Department, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, 14080, Mexico
Robinson Robles-Hernández
Tobacco Smoking and COPD Research Department, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, 14080, Mexico
Rafael de Jesús Hernández-Zenteno
Tobacco Smoking and COPD Research Department, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, 14080, Mexico
Daniela Valencia-Pérez Rea
HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, 14080, Mexico
Brandon Bautista-Becerril
HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, 14080, Mexico
María Elena Ramírez-Díaz
Coordinación de Vigilancia Epidemiológica, Jurisdicción 06 Sierra, Tlacolula de Matamoros Oaxaca, Servicios de Salud de Oaxaca, Oaxaca, 70400, Mexico
Filiberto Cruz-Vicente
Internal Medicine Department, Hospital Civil Aurelio Valdivieso, Servicios de Salud de Oaxaca, Oaxaca, 68050, Mexico
María de Lourdes Martínez-Gómez
Hospital Regional de Alta Especialidad de Oaxaca, Oaxaca, 71256, Mexico
Raúl Sansores
Clínica de Enfermedades Respiratorias, Fundación Médica Sur, Mexico City, 14080, Mexico
Ramcés Falfán-Valencia
HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, 14080, Mexico; Corresponding author. HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas. Calzada de Tlalpan 4502, Sección XVI, Mexico City, 14080, Mexico.
The receptor for advanced glycation end products (RAGE) and its gene (AGER) have been related to lung injury and inflammatory diseases, including chronic obstructive pulmonary disease (COPD). We aimed to evaluate the association of rs2071288, rs3134940, rs184003, and rs2070600 AGER single-nucleotide variants and the soluble-RAGE plasma and sputum levels with COPD secondary to biomass-burning smoke (BBS) and tobacco smoking. Four groups, including 2189 subjects, were analyzed: COPD secondary to BBS exposure (COPD-BBS, n = 342), BBS-exposed subjects without COPD (BBES, n = 774), tobacco smoking-induced COPD (COPD-TS, n = 434), and smokers without COPD (SWOC, n = 639). Allelic discrimination assays determined the AGER variants. The sRAGE was quantified in plasma (n = 240) and induced-sputum (n = 72) samples from a subgroup of patients using the ELISA technique. In addition, a meta-analysis was performed for the association of rs2070600 with COPD susceptibility. None of the studied genetic variants were found to be associated with COPD-BBS or COPD-TS. A marginal association was observed for the rs3134940 with COPD-BBS (p = 0.066). The results from the meta-analysis, including six case-control studies (n = 4149 subjects), showed a lack of association of rs2070600 with COPD susceptibility (p = 0.681), probably due to interethnic differences. The sRAGE plasma levels were lower in COPD-BBS compared to BBS and in COPD-TS compared to SWOC. The sRAGE levels were also lower in sputum samples from COPD-BBS than BBES. Subjects with rs3134940-TC genotypes exhibit lower sRAGE plasma levels than TT subjects, mainly from the COPD-BBS and SWOC groups. The AGER variants were not associated with COPD-BBS nor COPD-TS, but the sRAGE plasma and sputum levels are related to both COPD-BBS and COPD-TS and are influenced by the rs3134940 variant.