title: SNPs in NRXN1 and CHRNA5 are associated to smoking and regulation of GABAergic and glutamatergic pathways.
abstract: To identify genetic variants associated with greater tobacco consumption in a Mexican population.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.affiliation: Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Laboratorio HLA, México, DF, México.|Instituto Mexicano del Seguro Social., Unidad de Investigación Médica en Inmunología, CMN S-XXI, México, DF, México.|Universidad Nacional Autónoma de México, Posgrado en Ciencias Biológicas, México, DF, México.
authors.forename: Gloria
authors.initials: G
authors.lastname: Pérez-Rubio
authors.affiliation: Instituto Mexicano del Seguro Social., Unidad de Investigación Médica en Inmunología, CMN S-XXI, México, DF, México.
authors.forename: Martha E
authors.initials: ME
authors.lastname: Pérez-Rodríguez
authors.affiliation: Instituto Nacional De Medicina Genómica, Departamento de Genómica Computacional, México, DF, México.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Fernández-López
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Departamento de Investigación en Tabaquismo y EPOC, México, DF, México.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Ramírez-Venegas
authors.affiliation: Universidad Nacional Autónoma de México, Campus Juriquilla, Instituto de Neurobiología, Departamento de Neurobiología Celular y Molecular, Juriquilla, Querétaro, Mexico.
authors.forename: Jesús
authors.initials: J
authors.lastname: García-Colunga
authors.affiliation: Universidad Nacional Autónoma de México, Facultad de Estudios Superiores (FES)-Iztacala, Biomedicine Research Unit (UBIMED), Cancer Epigenomics Laboratory 12, Tlalnepantla, México, México.
authors.forename: Federico
authors.initials: F
authors.lastname: Ávila-Moreno
authors.affiliation: Universidad Nacional Autónoma de México, Posgrado en Ciencias Biológicas, México, DF, México.
authors.forename: Angel
authors.initials: A
authors.lastname: Camarena
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Departamento de Investigación en Tabaquismo y EPOC, México, DF, México.
authors.forename: Raúl H
authors.initials: RH
authors.lastname: Sansores
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Laboratorio HLA, México, DF, México.
authors.forename: Ramcés
authors.initials: R
authors.lastname: Falfán-Valencia
mesh_terms: D000328:Adult; D000368:Aged; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D006801:Humans; D008297:Male; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D019006:Neural Cell Adhesion Molecules; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D025341:Principal Component Analysis / Q000379:methods; D018079:Receptors, GABA / Q000502:physiology*; D017470:Receptors, Glutamate / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000235:genetics*; D012907:Smoking / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy; D016540:Smoking Cessation / Q000379:methods
chemical_list: C447158:CHRNA5 protein, human; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; C539628:NRXN1 protein, human; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D018079:Receptors, GABA; D017470:Receptors, Glutamate; D011978:Receptors, Nicotinic
keywords: CHRNA5; NRXN1; genetic; nicotine addiction