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.

A pilot study of single nucleotide polymorphisms in the interleukin-6 receptor and their effects on pre- and post-transplant serum mediator level and outcome after allogeneic stem cell transplantation

“…Immunological reconstitution after allotransplantation in adult patients usually takes several months , and a possible explanation for detecting this effect only after 2 years may thus be a difference in the immunological context at these two time‐points, caused possibly by the delayed immune reconstitution. This SNP has been reported previously to influence the response to IL‐6 inhibition and has also been linked to the severity of chronic inflammatory disease . Unfortunately, due to the low allele frequency for this SNP, an analysis of its possible effect on cGVHD was not possible.…”

Polymorphisms in HTR2A and DRD4 Predispose to Smoking and Smoking Quantity

“…The deviations to the HWE can be due to several reasons; one of them is the structure of the population [26]. Mexican mestizo population is relatively young, consists of a mixture of different ethnic groups and European Caucasians; in previous studies [27] we have evaluated and reported population ancestry of individuals included in this study and have found that among the group of cases and controls there are not statistically significant population differences; with this knowledge, the test of HWE is necessary but is not sufficient [28,29] to think that data obtained for the rs6313 are not valid, especially because it is the genetic variable that is replicated in several populations. If this polymorphism is excluded for failing to meet HWE we would be discarding an important result that not only has been associated in other populations, it has been observed that the presence of the risk allele affects gene expression and even being regulated at the level of methylation.…”

Genetic variants in IL17A and serum levels of IL-17A are associated with COPD related to tobacco smoking and biomass burning

“…An imbalance in protease -antiprotease (α-1 antitrypsin deficiency) has been reported as one of the most important genetic factors associated with the presence of this entity 4 . Furthermore, single nucleotide polymorphisms (SNPs) in proinflammatory genes, such as TNF, CXCR2, CXCL8, ADAM19, and IL6R, have been described as an important risk factor for COPD and its severity [5][6][7] .…”