Gloria Pérez-Rubio1,2,3, Martha E Pérez-Rodríguez2, Juan Carlos Fernández-López4, Alejandra Ramírez-Venegas5, Jesús García-Colunga6, Federico Ávila-Moreno7, Angel Camarena3, Raúl H Sansores5, Ramcés Falfán-Valencia1. 1. Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Laboratorio HLA, México, DF, México. 2. Instituto Mexicano del Seguro Social., Unidad de Investigación Médica en Inmunología, CMN S-XXI, México, DF, México. 3. Universidad Nacional Autónoma de México, Posgrado en Ciencias Biológicas, México, DF, México. 4. Instituto Nacional De Medicina Genómica, Departamento de Genómica Computacional, México, DF, México. 5. Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Departamento de Investigación en Tabaquismo y EPOC, México, DF, México. 6. Universidad Nacional Autónoma de México, Campus Juriquilla, Instituto de Neurobiología, Departamento de Neurobiología Celular y Molecular, Juriquilla, Querétaro, Mexico. 7. Universidad Nacional Autónoma de México, Facultad de Estudios Superiores (FES)-Iztacala, Biomedicine Research Unit (UBIMED), Cancer Epigenomics Laboratory 12, Tlalnepantla, México, México.
Abstract
AIM: To identify genetic variants associated with greater tobacco consumption in a Mexican population. PATIENTS & METHODS: Daily smokers were classified as light smokers (LS; n = 742), heavy smokers (HS; n = 601) and nonsmokers (NS; n = 606). In the first stage, a genotyping microarray that included 347 SNPs in CHRNA2-CHRNA7/CHRNA10, CHRNB2-CHRNB4 and NRXN1 genes and 37 ancestry-informative markers was used to analyze 707 samples (187 HS, 328 LS and 192 NS). In the second stage, 14 SNPs from stage 1 were validated in the remaining samples (HS, LS and NS; n = 414 in each group) using real-time PCR. To predict the role of the associated SNPs, an in silico analysis was performed. RESULTS: Two SNPs in NRXN1 and two in CHRNA5 were associated with cigarette consumption, while rs10865246/C (NRXN1) was associated with high nicotine addiction. The in silico analysis revealed that rs1882296/T had a high level of homology with Hsa-miR-6740-5p, which encodes a putative miRNA that targets glutamate receptor subunits (GRIA2, GRID2) and GABA receptor subunits (GABRG1, GABRA4, GABRB2), while rs1882296/C had a high level of homology with Hsa-miR-6866-5p, which encodes a different miRNA that targets GRID2 and GABRB2. CONCLUSION: In a Mexican Mestizo population, greater consumption of cigarettes was influenced by polymorphisms in the NRXN1 and CHRNA5 genes. We proposed new hypotheses regarding the putative roles of miRNAs that influence the GABAergic and glutamatergic pathways in smoking addiction.
AIM: To identify genetic variants associated with greater tobacco consumption in a Mexican population. PATIENTS & METHODS: Daily smokers were classified as light smokers (LS; n = 742), heavy smokers (HS; n = 601) and nonsmokers (NS; n = 606). In the first stage, a genotyping microarray that included 347 SNPs in CHRNA2-CHRNA7/CHRNA10, CHRNB2-CHRNB4 and NRXN1 genes and 37 ancestry-informative markers was used to analyze 707 samples (187 HS, 328 LS and 192 NS). In the second stage, 14 SNPs from stage 1 were validated in the remaining samples (HS, LS and NS; n = 414 in each group) using real-time PCR. To predict the role of the associated SNPs, an in silico analysis was performed. RESULTS: Two SNPs in NRXN1 and two in CHRNA5 were associated with cigarette consumption, while rs10865246/C (NRXN1) was associated with high nicotine addiction. The in silico analysis revealed that rs1882296/T had a high level of homology with Hsa-miR-6740-5p, which encodes a putative miRNA that targets glutamate receptor subunits (GRIA2, GRID2) and GABA receptor subunits (GABRG1, GABRA4, GABRB2), while rs1882296/C had a high level of homology with Hsa-miR-6866-5p, which encodes a different miRNA that targets GRID2 and GABRB2. CONCLUSION: In a Mexican Mestizo population, greater consumption of cigarettes was influenced by polymorphisms in the NRXN1 and CHRNA5 genes. We proposed new hypotheses regarding the putative roles of miRNAs that influence the GABAergic and glutamatergic pathways in smoking addiction.
Authors: Hassan A Aziz; Abdel-Salam G Abdel-Salam; Mohammed A I Al-Obaide; Hytham W Alobydi; Saif Al-Humaish Journal: Front Genet Date: 2018-06-13 Impact factor: 4.599
Authors: Gloria Pérez-Rubio; Luis Alberto López-Flores; Alejandra Ramírez-Venegas; Raúl H Sansores; Ramcés Falfán-Valencia Journal: Data Brief Date: 2019-04-17
Authors: Luis A López-Flores; Gloria Pérez-Rubio; Alejandra Ramírez-Venegas; Enrique Ambrocio-Ortiz; Raúl H Sansores; Ramcés Falfán-Valencia Journal: Data Brief Date: 2017-09-13
Authors: Gloria Pérez-Rubio; Enrique Ambrocio-Ortiz; Luis A López-Flores; Ana I Juárez-Martín; Luis Octavio Jiménez-Valverde; Susana Zoreque-Cabrera; Gustavo Galicia-Negrete; María Elena Ramírez-Díaz; Filiberto Cruz-Vicente; Manuel de Jesús Castillejos-López; Citlaltepetl Salinas-Lara; Rafael de Jesús Hernández-Zenteno; Alejandra Ramírez-Venegas; Ramcés Falfán-Valencia Journal: Int J Chron Obstruct Pulmon Dis Date: 2020-05-27
Authors: Gloria Pérez-Rubio; Ramcés Falfán-Valencia; Juan Carlos Fernández-López; Alejandra Ramírez-Venegas; Rafael de Jesús Hernández-Zenteno; Fernando Flores-Trujillo; Irma Silva-Zolezzi Journal: Diagnostics (Basel) Date: 2021-03-27
Authors: Gloria Pérez-Rubio; Luis Alberto López-Flores; Ana Paula Cupertino; Francisco Cartujano-Barrera; Luz Myriam Reynales-Shigematsu; Mariana Ramírez; Edward F Ellerbeck; Rosibel Rodríguez-Bolaños; Ramcés Falfan-Valencia Journal: Int J Environ Res Public Health Date: 2021-06-19 Impact factor: 3.390