title: Genetic Variants in IL6R and ADAM19 are Associated with COPD Severity in a Mexican Mestizo Population.
abstract: Chronic obstructive pulmonary disease (COPD) is a complex and multifactorial disease with a strong genetic component. Our objective is to identify the genetic variants associated with COPD risk and its severity in Mexican Mestizo population. We evaluated 1285 single-nucleotide polymorphisms (SNPs) of candidate genes in 299 smokers with COPD (COPD-S) and 531 smokers without COPD (SWOC) using an Illumina GoldenGate genotyping microarray. In addition, 251 ancestry informative markers were included. Allele A of rs2545771 in CYP2F2P is associated with a lower risk of COPD (p = 4.02E-10, odds ratio [OR] = 0.104, confidence interval [CI] 95% 0.05-0.18). When the COPD group was stratified by severity according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD; levels III + IV vs. I + II), 3 SNPs (rs4329505 and rs4845626 in interleukin 6 receptor [IL6R] and rs1422794 in a disintegrin and metalloproteinase domain 19 [ADAM19]) were associated with a lower risk of suffering the most severe stages of the disease. rs2819096 in the surfactant protein D (SFTPD) gene was associated with a higher risk of COPD GOLD III + IV (p = 7.79E-03, OR = 1.80, CI 95% 1.16-2.79). Finally, the haplotype in IL6R was associated with a lower risk of suffering from more severe COPD, whereas the haplotype in ADAM19 was associated with a higher risk (p = 7.40E-03, OR = 2.83, CI 95% 1.20-6.86) of suffering from the severe stages of the disease. Our data suggest that there are alleles and haplotypes in the IL6R, ADAM19, and SFTPD genes associated with different severity stages of COPD; in CYP2F2P, rs25455771 is associated with a lower risk of COPD.
authors.affiliation: a Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas , México D. F. , México.|b Posgrado en Ciencias Biológicas , Universidad Nacional Autónoma de México , México D. F. , México.
authors.forename: Gloria
authors.initials: G
authors.lastname: Pérez-Rubio
authors.affiliation: c Instituto Nacional de Medicina Genómica , México , D. F. , México.
authors.forename: Irma
authors.initials: I
authors.lastname: Silva-Zolezzi
authors.affiliation: c Instituto Nacional de Medicina Genómica , México , D. F. , México.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Fernández-López
authors.affiliation: a Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas , México D. F. , México.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Camarena
authors.affiliation: a Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas , México D. F. , México.
authors.forename: Mónica
authors.initials: M
authors.lastname: Velázquez-Uncal
authors.affiliation: c Instituto Nacional de Medicina Genómica , México , D. F. , México.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Morales-Mandujano
authors.affiliation: a Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas , México D. F. , México.
authors.forename: Rafael De Jesús
authors.initials: Rde J
authors.lastname: Hernández-Zenteno
authors.affiliation: a Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas , México D. F. , México.
authors.forename: Fernando
authors.initials: F
authors.lastname: Flores-Trujillo
authors.affiliation: a Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas , México D. F. , México.
authors.forename: Candelaria
authors.initials: C
authors.lastname: Sánchez-Romero
authors.affiliation: a Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas , México D. F. , México.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Velázquez-Montero
authors.affiliation: a Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas , México D. F. , México.
authors.forename: Carlos
authors.initials: C
authors.lastname: Espinosa de Los Monteros
authors.affiliation: a Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas , México D. F. , México.
authors.forename: Raúl H
authors.initials: RH
authors.lastname: Sansores
authors.affiliation: a Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas , México D. F. , México.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Ramírez-Venegas
authors.affiliation: a Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas , México D. F. , México.
authors.forename: Ramcés
authors.initials: R
authors.lastname: Falfán-Valencia
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D008800:Mexico; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics* / Q000503:physiopathology; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics*; D019947:Receptors, Interleukin-6 / Q000235:genetics*; D012720:Severity of Illness Index; D012907:Smoking / Q000235:genetics
chemical_list: C508603:IL6R protein, human; D037663:Pulmonary Surfactant-Associated Protein D; D019947:Receptors, Interleukin-6; D003577:Cytochrome P-450 Enzyme System; D051722:ADAM Proteins; C411902:ADAM19 protein, human
keywords: Candidate gene; GOLD; Genetic association; SNPs