Genetic Variants in <i>IL6R</i> and <i>ADAM19</i> are Associated with COPD Severity in a Mexican Mestizo Population

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 <i>CYP2F2P</i> is associated with a lower risk of COPD (<i>p</i> = 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 <i>vs</i>. I + II), 3 SNPs (rs4329505 and rs4845626 in <i>interleukin 6 receptor [IL6R</i>] and rs1422794 in <i>a disintegrin and metalloproteinase domain 19 [ADAM19</i>]) were associated with a lower risk of suffering the most severe stages of the disease. rs2819096 in the <i>surfactant protein D</i> (<i>SFTPD</i>) gene was associated with a higher risk of COPD GOLD III + IV (<i>p</i> = 7.79E-03, OR = 1.80, CI 95% 1.16–2.79). Finally, the haplotype in <i>IL6R</i> was associated with a lower risk of suffering from more severe COPD, whereas the haplotype in <i>ADAM19</i> was associated with a higher risk (<i>p</i> = 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 <i>IL6R, ADAM19,</i> and <i>SFTPD</i> genes associated with different severity stages of COPD; in <i>CYP2F2P</i>, rs25455771 is associated with a lower risk of COPD.