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Identification of genetic variants in the TNF promoter associated with COPD secondary to tobacco smoking and its severity

Authors Reséndiz-Hernández JM, Sansores RH, Hernández-Zenteno RJ, Vargas-Alarcón G, Colín-Barenque L, Velázquez-Uncal M, Camarena A, Ramírez-Venegas A, Falfán-Valencia R

Received 21 February 2015

Accepted for publication 22 April 2015

Published 29 June 2015 Volume 2015:10(1) Pages 1241—1251

DOI https://doi.org/10.2147/COPD.S83298

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Richard Russell

Juan Manuel Reséndiz-Hernández,1,2 Raúl H Sansores,3 Rafael de Jesús Hernández-Zenteno,3 Gilberto Vargas-Alarcón,4 Laura Colín-Barenque,5 Mónica Velázquez-Uncal,3 Angel Camarena,1 Alejandra Ramírez-Venegas,3 Ramcés Falfán-Valencia1

1Laboratory HLA, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico; 2Graduate Program in Biological Sciences, Universidad Nacional Autónoma de México, Mexico City, Mexico; 3Research Department in smoking and COPD, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico; 4Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico; 5Department of Neuroscience, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla de Baz, Mexico State, Mexico

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.

Keywords: lung, cigarette smoking, SNP, GOLD, Mexican population

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