title: Identification of genetic variants in the TNF promoter associated with COPD secondary to tobacco smoking and its severity.
abstract: Chronic obstructive pulmonary disease (COPD) is an inflammatory disease that arises in response to noxious particles or gases. Associations of genetic polymorphisms in TNF have been reported in Asians and Caucasians, but not in Mestizo populations. A case-control study was conducted in two stages: in the first stage, patients with COPD (COPD group, n=165) and smokers without disease (SNC group, n=165) were included and the TNF promoter sequence was determined using direct sequencing. In the second stage, the identified polymorphisms were validated by real-time polymerase chain reaction (PCR) in COPD (n=260) and SNC (n=506). In the first stage, 11 different sets of "contig" alignments were determined, of which contig 10 was found to be associated with susceptibility (P=5.0E-04, OR [odds ratio] =3.64) and contig 1 with Global Initiative for COPD (GOLD) greater grade (P=1.0E-02, OR =3.82). The single nucleotide polymorphisms found in this region were individually identified; the GA genotypes of rs1800629 (P=0.038, OR =2.07), rs56036015 (P=0.0082, OR =3.18), and rs361525 (P=1.0E-02, OR =4.220) were higher in the COPD group vs the SNC group; after second-stage validation, rs1800629 (P=6.00E-03, OR =2.26) and rs56036015 (P=1.10E-03, OR =2.54) are maintained. There are genetic variants in the TNF promoter associated with increased risk of COPD secondary to smoking and with a higher GOLD grade in the Mexican Mestizo population.
authors.affiliation: Laboratory HLA, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico ; Graduate Program in Biological Sciences, Universidad Nacional Autónoma de México, Mexico City, Mexico.
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Reséndiz-Hernández
authors.affiliation: Research Department in smoking and COPD, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico.
authors.forename: Raúl H
authors.initials: RH
authors.lastname: Sansores
authors.affiliation: Research Department in smoking and COPD, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico.
authors.forename: Rafael de Jesús
authors.initials: Rde J
authors.lastname: Hernández-Zenteno
authors.affiliation: Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
authors.forename: Gilber
authors.initials: G
authors.lastname: Vargas-Alarcón
authors.affiliation: Department of Neuroscience, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla de Baz, Mexico State, Mexico.
authors.forename: Laura
authors.initials: L
authors.lastname: Colín-Barenque
authors.affiliation: Research Department in smoking and COPD, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico.
authors.forename: Mónica
authors.initials: M
authors.lastname: Velázquez-Uncal
authors.affiliation: Laboratory HLA, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico.
authors.forename: Angel
authors.initials: A
authors.lastname: Camarena
authors.affiliation: Research Department in smoking and COPD, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Ramírez-Venegas
authors.affiliation: Laboratory HLA, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico.
authors.forename: Ramcés
authors.initials: R
authors.lastname: Falfán-Valencia
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005541:Forced Expiratory Volume; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D008168:Lung / Q000503:physiopathology; D008297:Male; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D012720:Severity of Illness Index; D012907:Smoking / Q000009:adverse effects* / Q000208:ethnology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D014797:Vital Capacity
chemical_list: D014409:Tumor Necrosis Factor-alpha
keywords: GOLD; Mexican population; SNP; cigarette smoking; lung