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Purpose The protease inhibitor S (PiS) and Z (PiZ) variants have been stated as the only genetic cause of chronic obstructive pulmonary disease (COPD) in Caucasians. However, its frequency in admixed populations is low. We aimed to identify genetic susceptibility between PiS (rs17580) and PiZ (rs28929474) polymorphisms with COPD related to tobacco smoking and biomass-burning smoke as well as to determine its frequencies in Mestizo and Amerindian populations from Mexico. Patients and Methods One thousand and eight hundred seventy-eight subjects were included in two comparisons of cases and controls, (1) smokers with and without COPD (COPD-S, n=399; SWOC, n=1106); (2) Biomass-burning smoke-exposed subjects with and without COPD (COPD-BS, n=98; BBES, n=275). In addition, 2354 Mexican subjects identified as Mestizos (n=1952) and Amerindian (n=402) were included. The population structure was evaluated using 59 informative ancestry markers. Results The AT genotype of rs17580 is associated with COPD in both comparisons (COPD-S vs SWOC p

Background: Genetic association studies have identified single nucleotide polymorphisms (SNPs) associated with lasting lung diseases such as Chronic Obstructive Pulmonary Disease (COPD) and Idiopathic Pulmonary Fibrosis (IPF), as well as the simultaneous presentation, known as Combined Pulmonary Fibrosis and Emphysema (CPFE) Syndrome. It is unknown if these diseases share genetic variants previously described in an independent way. This study aims to identify common or differential variants between COPD, IPF, and CPFE.Materials and methods: The association analysis was carried out through a case-control design in a Mexican mestizo population (n = 828); three patients' groups were included: COPD smokers (COPD-S, n = 178), IPF patients (n = 93), and CPFE patients (n = 16). Also, two comparison groups were analyzed: smokers without COPD (SWOC, n = 367) and healthy subjects belonging to the Mexican Pulmonary Aging Cohort (PAC, n = 174). Five SNPs in four genes previously associated to interstitial and obstructive diseases were selected: rs2609255 (FAM13A), rs2736100 (TERT), rs2076295 (DSP) rs5743890, and rs111521887 (TOLLIP). Genotyping was performed by qPCR using predesigned Taqman probes.Results: In comparing IPF vs. PAC, significant differences were found in the frequency of the rs260955 G allele associated with the IPF risk (OR = 1.68, p = 0.01). Also, the genotypes, GG of rs260955 (OR = 2.86, p = 0.01) and TT of rs2076295 (OR = 1.79, p = 0.03) were associated with an increased risk of IPF; after adjusting by covariables, only the rs260955 G allele remain significant (p = 0.01). For the CPFE vs. PAC comparison, an increased CPFE risk was identified since there is a difference in the rs2736100 C allele (OR = 4.02, p < 0.01; adjusted p < 0.01). For COPD-S, the rs2609255 TG genotype was associated with increased COPD risk after adjusting by covariables.Conclusion: The rs2736100 C allele is associated with decreased IPF risk and confers an increased risk for CPFE. Also, the rs2076295 TT genotype is associated with increased IPF risk, while the GG genotype is associated with CFPE susceptibility. The rs2609255 G allele and GG genotype are associated with IPF susceptibility, while the TG genotype is present in patients with emphysema.

Background: Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory disease characterized by airflow obstruction, commonly present in smokers and subjects exposed to noxious particles product of biomass-burning smoke (BBS). Several association studies have identified single-nucleotide polymorphisms (SNP) in coding genes related to the heat shock proteins family-genes that codify the heat shock proteins (Hsp). Hsp accomplishes critical roles in regulating immune response, antigen-processing, eliminating protein aggregates and co-activating receptors. The presence of SNPs in these genes can lead to alterations in immune responses. We aimed to evaluate the association of SNPs in the HSP90 gene complex and COPD. Methods: We enrolled 1549 participants, divided into two comparison groups, 919 tobacco-smoking subjects (cases COPD-TS n = 294 and, controls SWOC n = 625) and 630 chronic exposed to BBS (cases COPD-BBS n = 186 and controls BBES n = 444). We genotyped 2 SNPs: the rs13296 in HSP90AB1 and rs2070908 in HSP90B1. Results: Through the dominant model (GC + CC), the rs2070908 is associated with decreased risk (p &lt, 0.01, OR = 0.6) to suffer COPD among chronic exposed BBS subjects. We found an association between rs13296 GG genotype and lower risk (p = 0.01, OR = 0.22) to suffer severe COPD-TS forms in the severity analysis. Conclusions: single-nucleotide variants in the HSP90AB1 and HSP90B1 genes are associated with decreased COPD risk in subjects exposed to BBS and the most severe forms of COPD in tobacco-smoking subjects.

Angiotensin-Converting Enzyme 2 (ACE2) is an 805 amino acid protein encoded by the ACE2 gene expressed in various human cells, especially in those located in the epithelia. The primary function of ACE2 is to produce angiotensin (1–7) from angiotensin II (Ang II). The current research has described the importance of ACE2 and Ang (1–7) in alternative routes of the renin-angiotensin system (RAS) that promote the downregulation of fibrosis, inflammation, and oxidative stress processes in a great variety of diseases, such as hypertension, acute lung injury, liver cirrhosis, and kidney abnormalities. Investigations into the recent outbreak of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have revealed the importance of ACE2 during infection and its role in recognizing viral binding proteins through interactions with specific amino acids of this enzyme. Additionally, the ACE2 expression in several organs has allowed us to understand the clinical picture related to the infection caused by SARS-CoV-2. This review aims to provide context for the functions and importance of ACE2 with regards to SARS-CoV-2 in the general clinical aspect and its impact on other diseases, especially respiratory diseases.

Although different trajectories in lung function decline have been identified in patients with COPD associated to tobacco exposure (TE-COPD), genetic, environmental, and infectious factors affecting lung function throughout life have not been fully elucidated in patients with COPD associated to biomass (BE-COPD). In this review, we present current epidemiological findings and notable advances in the natural history of lung decline in BE-COPD, as well as conditions modeling the FEV1trajectory, such as health insults, during the first years of childhood. Evidence shows that women exposed to biomass smoke reach adult life with a lower FEV1than expected. However, in contrast to the “horse racing effect” predicting an excessive lung-function decline in forthcoming years, as observed in smokers, this decline is slower in non-smokers, and no rapid decliners are observed. Accordingly, BE-COPD might be considered another phenotype of COPD based on assessments of lung function decline. Likewise, other functional and clinical aspects described in this review suggest that this condition might be similar to TE-COPD. More research is needed to fully characterize this subgroup of variants of COPD.

Genetic variability influences the susceptibility to and severity of complex diseases, there is a lower risk of COPD in Hispanics than in non-Hispanic Caucasians. In this study, we included 830 Mexican-Mestizo subjects, 299 were patients with COPD secondary to tobacco smoking, and 531 were smokers without COPD. We employed a customized genotyping array of single nucleotide polymorphisms (SNPs). The population structure was evaluated by principal component analysis and allele association through a logistic regression model and haplotype identification. In this study, 118 individuals were identified with a high Caucasian component and 712 with a high Amerindian component. Independent of the ancestral contribution, two SNPs were associated with a reduced risk (p ≤ 0.01) of developing COPD in the CYP2A6 (rs4105144) and CYP2B6 (rs10426235) genes, however, a haplotype was associated with an increased risk of COPD (p = 0.007, OR = 2.47) in the CHRNA5-CHRNA3 loci among smokers with a high Caucasian component. In Mexican-Mestizo smokers, there are SNPs in genes that encode proteins responsible for the metabolism of nicotine associated with a lower risk of COPD, individuals with a high Caucasian component harboring a haplotype in the CHRNA5-CHRNA3 loci have a higher risk of suffering from COPD.

The antisynthetase syndrome (ASSD) is an autoimmune disorder characterized by myositis, arthritis, mechanic's hands, fever, Raynaud phenomenon, and interstitial lung disease (ILD). We aimed to evaluate single-nucleotide polymorphisms in the interleukin 1B (IL1B) gene and their association between ILD with antisynthetase autoantibodies, as well as IL-1β serum levels. The most frequent antisynthetase autoantibody was anti-Jo1. The most frequent tomographic pattern was non-specific interstitial pneumonia, whereas in the anti-Jo1 subjects, it was organized pneumonia. Anti-Jo1 patients tend to have more significant arthritis, and Raynaud phenomenon have higher levels of creatinine phosphokinase. In the IL1B gene, the GG genotype and G allele of rs1143634 [odds ratio (OR) = 2.21 and OR = 2.60, respectively, p < 0.05] are associated with an increased risk, as well as with the dominant and recessive models (p < 0.05). This finding is maintained after logistic regression analysis adjusting for potential confounding variables (p < 0.05). Subjects with the rs16944/AG heterozygous genotype had higher serum levels of IL-1β compared to homozygous (p < 0.05). In conclusion, rs1143634 is associated with a higher risk of ASSD. Also, the GA genotype is associated with higher levels of IL-1β in ASSD patients.

Due to its immunomodulatory effects and the limitation in the radiological damage progression, disease-modifying antirheumatic drugs (DMARDs) work as first-line rheumatoid arthritis (RA) treatment. In recent years, numerous research projects have suggested that the metabolism of DMARDs could have a role in gut dysbiosis, which indicates that the microbiota variability could modify the employment of direct and indirect mechanisms in the response to treatment. The main objective of this review was to understand the gut microbiota bacterial variability in patients with RA, pre and post-treatment with DMARDs, and to identify the possible mechanisms through which microbiota can regulate the response to pharmacological therapy.

Background Genetic association studies have identified single nucleotide polymorphisms (SNPs) related to chronic obstructive pulmonary disease (COPD) susceptibility. The aim of this study was to identify HHIP genetic variants associated with COPD, pulmonary function, and serum and sputum HHIP protein levels in Mexican mestizo smokers. Materials and Methods Association analysis was performed by carrying out a case-control study in Mexican mestizo smokers comprised of two groups: tobacco-smoking subjects with COPD (COPD-TS, n = 222) and smokers without COPD (SWOC, n = 333). We evaluated three SNPs (rs13147758, rs1828591, and rs13118928) in the HHIP gene. Allele discrimination was accomplished by qPCR using TaqMan probes, and determination of protein levels in the serum and sputum supernatants (SS) was performed using ELISA. Results Statistically significant differences were observed in the rs13147758 GG genotype (adjusted p = 0.014, OR = 1.95) and the rs13147758-rs1828591 GA haplotype (p = 6.6E-06, OR = 2.65) in the case-control comparison. HHIP protein levels were elevated in SS samples from the COPD-TS group compared to those from the SWOC group (p = 0.03). Based on genotype analysis, HHIP protein levels were lower in the serum samples of rs13147758 GG genotype carriers in the COPD-TS group than in the serum samples of rs13147758 GG genotype carriers from the SWOC group (p < 0.05), but there were no differences in the sputum samples. Conclusion The rs13147758 GG genotype and the rs13147758-rs1828591 GA haplotype are associated with susceptibility to COPD. Furthermore, an association in protein levels was observed between the HHIP rs13147758 genotype and COPD in Mexican mestizo smokers.

Background: A variety of organic materials (biomass) are burned for cooking and heating purposes in poorly ventilated houses, smoke from biomass combustion is considered an environmental risk factor for chronic obstructive pulmonary disease COPD. In this study, we attempted to determine the participation of single-nucleotide variants in the HHIP (hedgehog-interacting protein) gene in lung function, HHIP serum levels, and HHIP sputum supernatant levels in Mexican women with and without COPD who were exposed to biomass-burning smoke. Methods: In a case-control study (COPD-BS, n = 186, BBES, n = 557) in Mexican women, three SNPs (rs13147758, rs1828591, and rs13118928) in the HHIP gene were analyzed by qPCR, serum and supernatant sputum protein levels were determined through ELISA. Results: The rs13118928 GG genotype is associated with decreased risk (p = 0.021, OR = 0.51, CI95% = 0.27&ndash, 0.97) and the recessive genetic model (p = 0.0023), the rs1828591-rs13118928 GG haplotype is also associated with decreased risk (p = 0.04, OR = 0.65, CI95% 0.43&ndash, 0.98). By the dominant model (rs13118928), the subjects with one or two copies of the minor allele (G) exhibited higher protein levels. Additionally, two correlations with the AG genotype were identified: BBES with FEV1 (p = 0.03, r2 = 0.53) and COPD-BS with FEV1/FVC (p = 0.012, r2 = 0.54). Conclusions: Single-nucleotide variants in the HHIP gene are associated with decreased COPD risk, higher HHIP serum levels, and better lung function in Mexican women exposed to biomass burning.

The lung microbiome composition has critical implications in the regulation of innate and adaptive immune responses. Next-generation sequencing techniques have revolutionized the understanding of pulmonary physiology and pathology. Currently, it is clear that the lung is not a sterile place; therefore, the investigation of the participation of the pulmonary microbiome in the presentation, severity, and prognosis of multiple pathologies, such as asthma, chronic obstructive pulmonary disease, and interstitial lung diseases, contributes to a better understanding of the pathophysiology. Dysregulation of microbiota components in the microbiome–host interaction is associated with multiple lung pathologies, severity, and prognosis, making microbiome study a useful tool for the identification of potential therapeutic strategies. This review integrates the findings regarding the activation and regulation of the innate and adaptive immune response pathways according to the microbiome, including microbial patterns that could be characteristic of certain diseases. Further studies are required to verify whether the microbial profile and its metabolites can be used as biomarkers of disease progression or poor prognosis and to identify new therapeutic targets that restore lung dysbiosis safely and effectively.

Chronic obstructive pulmonary disease (COPD) is a complex and multifactorial disease involving systemic inflammation. Although certain genetic components have been implicated in the development and progression of this disease, few studies have examined the participation of polymorphisms in proinflammatory genes and the extent to which polymorphisms are related to plasma levels of cytokines involved in the inflammatory process.Of the 1125 smokers participating in the study, 438 had COPD, and 687 did not. We determined the genotype of 5 SNPs distributed in the genes: IL6, CXL8, CSF2, CCL1 and IL1B. The plasma protein expression of these genes was also evaluated and categorized according to genotype and the severity of COPD (GOLD grade).An analysis using the codominant model showed an association between rs1818879 in IL6 and susceptibility to COPD (GA OR = 1.1, AA OR = 1.77; p 0.01), as well as an association between rs25882 in CSF2 and a greater severity of the disease (TC OR = 1.84, CC OR = 3.62; p 0.01). No association was found between the presence of certain alleles in the SNPs and the plasma levels of the corresponding proteins.There are genetic polymorphisms related to susceptibility to COPD (rs1818879/A in IL6), as well as to the risk of greater severity of the disease (rs25882/T in CSF2). The presence of the alleles of interest did not significantly affect plasma levels of the codified proteins.

Background Smoking and smoke from biomass burning (BB) are the main environmental risk factors for COPD. Clinical differences have been described between COPD related to smoking and related to wood smoke, but no studies have shown genetic differences between patients exposed to these two risk factors. Methods To investigate a possible association of tumor necrosis factor (TNF) promoter polymorphisms, we conducted a case-control study. A total of 1,322 subjects were included in four groups: patients with a diagnosis of COPD secondary to smoking (COPD-S, n=384), patients with COPD secondary to biomass burning (COPD-BB, n=168), smokers without COPD (SWOC, n=674), and biomass burning-exposed subjects (BBES n=96). Additionally, a group of 950 Mexican mestizos (MMs) was included as a population control. Three single nucleotide polymorphisms (SNPs) were selected in the TNF gene (rs1800629, rs361525, and rs1800750) and one SNP in the lymphotoxin alpha gene (rs909253). Results Statistically significant differences were found with genotype GA of the rs1800629: COPD-S vs SWOC, (p

IL-17A is an important pro-inflammatory cytokine involved in the inflammatory response in chronic obstructive pulmonary disease (COPD). To evaluate the role played by single nucleotide polymorphisms of IL17A and protein levels in susceptibility to COPD, 1,807 subjects were included in a case-control study; 436 had COPD related to tobacco smoking (COPD-S) and 190 had COPD related to biomass burning (COPD-BB). Six hundred fifty-seven smokers without COPD (SWOC) and 183 biomass burning-exposed subjects (BBES) served as the respective control groups. The CC genotype and C allele of rs8193036 were associated with COPD (COPD-S vs. SWOC: p vs. SWOC, COPD-S vs. COPD-BB, and SWOC vs. BBES (p vs. CC and TC vs. CC (p vs. SWOC with both polymorphisms evaluated (p vs. BBES but with a reduced risk of exacerbation (p IL17A are associated with COPD. Serum levels of IL-17A were higher in smokers with and without COPD.

Heat shock proteins (HSP) genes are a superfamily responsible for encoding highly conserved proteins that are important for antigen presentation, immune response regulation, and cellular housekeeping processes. These proteins can be increased by cellular stress related to pollution, for example, smoke from biomass burning and/or tobacco smoking. Single nucleotide polymorphisms (SNPs) in these genes could affect the levels of their proteins, as well as the susceptibility to developing lung diseases, such as chronic obstructive pulmonary disease (COPD), related to the exposure to environmental factors.Methods: The subjects included were organized into two comparison groups: 1,103 smokers (COPD patients, COPD-S = 360; smokers without COPD, SWOC = 743) and 442 never-smokers who were chronically exposed to biomass smoke (COPD patients, COPD-BS = 244; exposed without COPD, BBES = 198). Eight SNPs in three HSP genes were selected and genotyped: four in HSPA1A, two in HSPA1B, and two in HSPA1L. Sputum expectoration was induced to obtain pulmonary cells and relative quantification of mRNA expression. Subsequently, the intracellular protein levels of total Hsp27, phosphorylated Hsp27 (Hsp27p), Hsp60, and Hsp70 were measured in a sample of 148 individuals selected based on genotypes.Results: In the smokers’ group, by a dominant model analysis, we found associations between rs1008438 (CA+AA; p = 0.006, OR = 1.52), rs6457452 (CT+TT; p = 0.000015, OR = 1.99), and rs2763979 (CT+TT; p = 0.007, OR = 1.60) and the risk to COPD. Among those exposed to biomass-burning smoke, only rs1008438 (CA+AA; p < 0.01, OR = 2.84) was associated. Additionally, rs1008438 was associated with disease severity in the COPD-S group (AA; p = 0.02, OR = 2.09). An increase in the relative expression level of HSPA1A was found (12-fold change) in the COPD-BS over the BBES group. Differences in Hsp27 and Hsp60 proteins levels were found (p < 0.05) in the comparison of COPD-S vs. SWOC. Among biomass-burning smoke-exposed subjects, differences in the levels of all proteins (p < 0.05) were detected.Conclusion: SNPs in HSP genes are associated with the risk of COPD and severe forms of the disease. Differences in the intracellular Hsp levels are altered depending on the exposition source.

Cigarette smoking is influenced by nicotine&rsquo, s effects on dopaminergic activity, which appear to be moderated by genetic variation, particularly a variable number tandem repeat (VNTR, 48 bp) polymorphism in the third exon of the dopamine receptor gene (DRD4). Smokers with the VNTR &ge, 7 repeats (long, L allele) report markedly increased participation in some smoking behaviors, hence, our aim was to evaluate the association of the L allele in Mexican Mestizo smokers with and without COPD. The DRD4 VNTR 48 bp was genotyped in 492 Mexican Mestizo smokers: 164 COPD patients (&ge, 20 cigarettes per day, cpd), 164 heavy smokers without COPD (HS, &ge, 20 cpd) and 164 light smokers without COPD (LS, 1&ndash, 10 cpd). In the dominant model analysis (SL + LL vs. SS), men in the COPD and HS groups showed a statistical difference compared to LS (p = 0.01, OR = 2.06, CI 95% 1.17&ndash, 3.64 and p = 0.05, OR = 1.88, CI 95% 1.03&ndash, 3.45, respectively). In addition, by clustering smokers &gt, 20 cpd (COPD + HS) and comparing with the LS group, we found an association with increased risk of higher tobacco smoking p = 0.01, OR = 1.99, CI 95% 1.18&ndash, 3.34. In conclusion, the long allele (L) in the VNTR of the DRD4 gene is associated with the risk of presenting higher tobacco smoking in male Mexican Mestizo smokers.

Among hypersensitivity pneumonitis (HP) patients have been identified who develop autoantibodies with and without clinical manifestations of autoimmune disease. Genetic factors involved in this process and the effect of these autoantibodies on the clinical phenotype are unknown. Matrix metalloproteinases (MMPs) have an important role in architecture and pulmonary remodeling. The aim of our study was to identify polymorphisms in the MMP1, MMP2, MMP9 and MMP12 genes associated with susceptibility to HP with the presence of autoantibodies (HPAbs+). Using the dominant model of genetic association, comparisons were made between three groups. For rs7125062 in MMP1 (CC vs. CT+TT), we found an association when comparing groups of patients with healthy controls: HPAbs+ vs. HC (p &lt, 0.001, OR = 10.62, CI 95% = 4.34 &minus, 25.96), HP vs. HC (p &lt, 0.001, OR = 7.85, 95% CI 95% = 4.54 &minus, 13.57). This rs11646643 in MMP2 shows a difference in the HPAbs+ group by the dominant genetic model GG vs. GA+AA, (p = 0.001, OR = 8.11, CI 95% = 1.83 &minus, 35.84). In the linear regression analysis, rs11646643 was associated with a difference in basal forced vital capacity (FVC)/12 months (p = 0.013, = 0.228, 95% CI95% = 1.97 &minus, 16.72). We identified single-nucleotide polymorphisms (SNPs) associated with the risk of developing HP, and with the evolution towards the phenotype with the presence of autoantibodies. Also, to the decrease in plasma MMP-2 levels.

This article contains data on the allele and genotype frequency for single nucleotide polymorphisms (SNPs) in candidate genes CHRNA5 (rs16969968, rs17408276, rs680244) CHRNA3 (rs6495307, rs12914385) NRXN1 (rs10865246, rs1882296, rs985919) and HTR2A (rs6311, rs6313) previously evaluated as genetic risk variants for cigarette smoking at an early age and relapse to smoking cessation treatment Perez-Rubio et al., 2018. These SNPs were selected due to previous associations in other populations, including Mexican Mestizos. Smokers were classified according to the age at onset, cigarettes per day, nicotine dependence, COPD status and therapy received.

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.

Antisynthetase syndrome (ASSD) is a rare multisystemic connective tissue disease affecting the skin, joints, muscles, and lungs, characterized by anti-aminoacyl transfer-RNA-synthetases (anti-tRNA) autoantibodies production, being anti-Jo1 the most frequent. We included one-hundred twenty-one ASSD patients and 340 healthy subjects (HS), and also, we divided the case group into anti-Jo1 and non-anti-Jo1. Two single nucleotide polymorphisms (SNPs) in the IL17A gene were evaluated. Anti-Jo1 was the most common anti-tRNA antibody in our cohort, and the most frequent tomographic pattern was non-specific interstitial pneumonia (NSIP). Anti-Jo1 ASSD patients had higher levels of creatine phosphokinase than the non-anti-Jo1 group. Significant differences in genotype frequencies with rs8193036/CC between anti-Jo1 vs. non-anti-Jo1 ASSD patients (p &lt, 0.001), maintaining the association after Bonferroni correction (p = 0.002). Additionally, in the anti-Jo1 group vs. HS comparison, we found a statistically significant difference with the same SNP (p = 0.018, OR= 2.91, 95% CI = 1.15−7.35), maintaining the association after Bonferroni correction (p = 0.036). The rs8193036/CC genotype in IL17A is associated with ASSD patients with anti-Jo1. Also, anti-Jo1 and non-anti-Jo1 patients display differences in genotype frequencies.

Influenza A virus (IAV) is the most common infectious agent in humans, and infects approximately 10–20% of the world’s population, resulting in 3–5 million hospitalizations per year. A scientific literature search was performed using the PubMed database and the Medical Subject Headings (MeSH) “Influenza A H1N1” and “Genetic susceptibility”. Due to the amount of information and evidence about genetic susceptibility generated from the studies carried out in the last influenza A H1N1 pandemic, studies published between January 2009 to May 2020 were considered; 119 papers were found. Several pathways are involved in the host defense against IAV infection (innate immune response, pro-inflammatory cytokines, chemokines, complement activation, and HLA molecules participating in viral antigen presentation). On the other hand, single nucleotide polymorphisms (SNPs) are a type of variation involving the change of a single base pair that can mean that encoded proteins do not carry out their functions properly, allowing higher viral replication and abnormal host response to infection, such as a cytokine storm. Some of the most studied SNPs associated with IAV infection genetic susceptibility are located in the FCGR2A, C1QBP, CD55, and RPAIN genes, affecting host immune responses through abnormal complement activation. Also, SNPs in IFITM3 (which participates in endosomes and lysosomes fusion) represent some of the most critical polymorphisms associated with IAV infection, suggesting an ineffective virus clearance. Regarding inflammatory response genes, single nucleotide variants in IL1B, TNF, LTA IL17A, IL8, IL6, IRAK2, PIK3CG, and HLA complex are associated with altered phenotype in pro-inflammatory molecules, participating in IAV infection and the severest form of the disease.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality in developed countries. Although cigarette smoking is the major risk factor, only 10-20% of smokers develop COPD. The extent of cigarette smoking (pack-years and smoking duration) accounts for only 15% of the variation in lung function, indicating that differences in susceptibility to COPD must exist. We provide an overview of the complexity of nicotine addiction and COPD, with special attention to the involvement of genetic factors. The following aspects are discussed in the present article: (1) epidemiology in Mexico and (2) a review of the published literature on genetic association studies using the National Center for Biotechnology Information database of the United States as a search tool. COPD is unique among complex genetic diseases where an environmental risk factor is known and the level of exposure can be documented with some precision. The high morbidity and mortality associated with COPD and its chronic and progressive nature has prompted the use of molecular genetic studies to identify susceptibility factors for the disease. Biomedical research has a remarkable set of tools to aid in the discovery of genes and polymorphisms. We present a review of the most relevant genetic associations in nicotine addiction and COPD.

Anti-tRNA autoantibodies are associated with interstitial lung disease (ILD), in at least two clinical scenarios: the anti-synthetase syndrome (ASSD) and interstitial pneumonia with autoimmune features (IPAF). Under pathological conditions, cytokines indicate the participating elements and the course of inflammatory phenomena. We aimed to quantify serum concentrations of different inflammatory cytokines profiles in patients with anti-tRNA associated ILD (anti-tRNA-ILD) and estimate the association between these and ILD improvement and progression. Serum levels of 18 cytokines from baseline and after six months of treatment of ILD patients&rsquo, positives to anti-tRNA were included in the current study. At six months, patients were classified as with or without ILD progression. A total of 39 patients were included (10 anti-Jo1, eight anti-PL7, 11 anti-PL12, and 10 anti-Ej). Three patients (7.6%) had ILD progression (progressors patients, PP) and showed statistically higher levels in IL-4, IL-10, IL-17A, IL-22, GM-CSF, IL-1&beta, IL-6, IL-12, IL-18, and TNF-&alpha, compared to patients without disease progression (no progressors patients, NPP). IL-17A, IL-1&beta, and IL-6 (T-helper-lymphocyte (Th)17 inflammatory cytokine profile) were elevated and had a high discriminatory capacity in distinguishing ILD PP of those NPP at follow-up. Overall, there is an association between the cytokines of the Th17 inflammatory profile and the ASSD progression.

Background: Asthma is a complex and chronic inflammatory airway disease. Asthma&rsquo, s etiology is unknown, however, genetic and environmental factors could affect disease susceptibility. We designed a case-control study aimed to evaluate the role of single-nucleotide polymorphisms (SNP), and copy-number variants (CNV) in the IL4 and IL13 genes in asthma susceptibility and their participation in plasma cytokine levels depending on genotypes Methods: We include 486 subjects, divided into asthma patients (AP, n = 141) and clinically healthy subjects (CHS, n = 345). We genotyped three SNP, two in the IL4 and two in the IL13 gene, also, two CNVs in IL4. The IL-4, IL-13 and IgE plasma levels were quantified. Results: Biomass-burning smoke exposure was higher in the AP group compared to CHS (47.5% vs. 20.9%, p &lt, 0.01, OR = 3.4). No statistical differences were found in the genetic association analysis. In both CNV, we only found the common allele. For the analysis of IL-4, IL-13, and IgE measures stratified by genotypes, no significant association or correlation was found. Conclusion: In the Mexican-mestizo population, SNPs neither CNVs in IL4 nor IL13 are associated with asthma susceptibility or involved serum cytokine levels. Biomass-burning smoke is a risk factor in asthma susceptibility.

The pathogenesis of Rheumatoid Arthritis (RA) is not fully understood, probably influenced by genetic and environmental factors. Interstitial Lung Disease (ILD) is an extra-articular manifestation of RA, which contributes significantly to morbidity and mortality. The identification of anti-HLA antibodies has been useful in the transplantation field, however, its contribution to autoimmune diseases as RA has not been fully studied. We aimed to determine the presence of anti-HLA antibodies in RA patients with and without ILD and its possible association with clinical and biochemical markers. One-hundred and forty-seven RA patients, of which 65 had ILD (RA-ILD group), were included. Sera samples for Anti-HLA Class II LABScreen panel-reactive antibodies (PRA) were analyzed. In both groups, women predominated, and lung function was worse in patients with ILD. The anti-CCP+ (UI/mL) was higher in the RA group in comparison to RA-ILD (p &lt, 0.001). Expositional risk factors (tobacco smoking and biomass-burning smoke) were higher in RA-ILD patients. PRA+ was identified in ~25% RA-ILD patients, while ~29% in the RA group. The CRP levels have a positive correlation with the percentage of reactivity (%PRA, p = 0.02, r2 = 0.60) in the RA-ILD group. In conclusion, anti-HLA antibodies correlate with C-reactive protein levels in RA patients with ILD.

Background: In the last years it has been shown a subgroup of patients with hypersensitivity pneumonitis (HP) that develop autoantibodies with or without clinical manifestations of autoimmune disease. Factors involved in this process, and the effect of these autoantibodies on clinical course and mortality are unknown. Aim: To evaluate association between HLA class II alleles and HP patients with and without autoantibodies. Methods: 170 patients with confirmed diagnosis of HP were included. Autoimmune laboratory profile included ANA, RF, anti-SSA/Ro, anti-SSB/La, anti-Scl70 and anti-CCP. HLA typing was performed by PCR-SSP in a high-resolution modality, including HLA-DRB1 and HLA-DQB1 loci. Statistical analysis was performed employing EPI-info v7 and SPSSv20. Results: Sixty HP patients developed sera autoantibodies (HPAb+; 50 females; 53.4±9.3 years) and 110 HP patients did not (HP; 84 females; 52.5±11.8 years). The frequency of the allele HLA-DRB1*03 was remarkably increased in the HPAb+ group (10.8% vs. 0.45%; OR=26.6, CI95% 3.0-206.8 p=8.26E-06). Likewise, the loci HLA-DQB1*02:01 and DQB1*06:01 frequencies were almost three-fold higher in the HPAb+ group [(15.0% versus 6.4%, OR=2.59, CI95% 1.24-5.42; p=7.7E-03) and (12.5% vs. 4.5%, OR=3.33, CI95% 1.30-6.90 p=6.8E-03)]. Regarding the haplotypes, DRB1*03-DQB1*02:01 showed a significant difference (OR=17.75, CI95% 2.22-141.9 p=0.0004). Mortality was associated to the HLA-DRB1*03 allele (p=0.004, β=0.225, CI95% 0.098-0.505). Conclusions: A subset of HP patients present circulating autoantibodies which is associated, at least partially, to some variants of the HLA, increasing the risk for death.

Aspirin exacerbated respiratory disease (AERD) is a set of diseases of the unified airway, and its physiopathology is related to disruption of the metabolism of arachidonic acid (AA). Genetic association studies in AERD had explored single nucleotide polymorphism (SNPs) in several genes related to many mechanisms (AA metabolism, inflammation, drug metabolism, etc.) but most lack validation stages in second populations. Our aim is to evaluated whether contribution to susceptibility of SNPs reported in other populations are associated with AERD in Mexican Mestizo patients. We developed a replicative study in two stages. In the first, 381 SNPs selected by fine mapping of associated genes, (previously reported in the literature), were integrated into a microarray and tested in three groups (AERD, asthma and healthy controls -HC-) using the GoldenGate array. Results associated to risk based on genetic models [comparing: AERD vs. HC (comparison 1, C1), AERD vs. asthma (C2), and asthma vs. HC (C3)] were validated in the second stage in other population groups using qPCR. In the first stage, we identified 11 SNPs associated with risk in C1.The top SNPs were ACE-rs4309C (p = 0.0001) and MS4A2-rs573790C (p = 0.0002). In C2, we detected 14 SNPs, including ACE-rs4309C (p = 0.0001). In C3, we found MS4A2-rs573790C (p = 0.001). Using genetic models, C1 MS4A2-rs57370 CC (p = 0.001), and ACE-rs4309 CC (p = 0.002) had associations. In C2 ACE-rs4309 CC (p = 0.0001) and C3 MS4A2-rs573790 CC (p = 0.001) were also associate with risk. In the second stage, only MS4A2-rs573790 CC had significance in C1 and C3 (p = 0.008 and p = 0.03). We concluded that rs573790 in the MS4A2 gene is the only SNP that supports an association with AERD in Mexican Mestizo patients in both stages of the study.

Aspirin-exacerbated respiratory disease (AERD) refers to the combination of asthma rhinosinusitis and poliposis; ingestion of aspirin or other non-steroid anti-inflammatory drugs exacerbate asthma-like symptoms. The pathogenesis of AERD is unknown, and genetic and environmental factors contribute to the disease. Our objective is identifying polymorphisms associated with susceptibility in a Mexican mestizo population. Primarily we performed custom Illumina goldengate array-based genotyping of 1512 SNPs, carefully selected from a variety of acute/chronic inflammatory lung conditions previously reported. Four SNPs in TRPM3 gene showed the lowest p-values (rs10780946, rs7025694, rs1889915, and rs7047645). We further selected rs10780946 and rs7025694 for validation using Taqman genotyping (n = 743; 288 AERD, 272 ATA, and 183 HC). rs10780946 showed association when compared between AERD and ATA groups under co-dominant (p = 0.006), dominant (p = 0.002), overdominant (p = 0.01), and log-additive (p = 0.03) genetic models. AERD showed increased heterozygous TC (rs10780946–rs7025694) haplotype compared to ATA and HC (p

Aim: To evaluate association of single nucleotide polymorphisms (SNPs) in the MMP1, MMP2, MMP9 and MMP12 genes and serum MMP-2 and MMP-9 levels in smoking chronic obstructive pulmonary disease (COPD) patients. Materials & methods: Genotyping using real-time PCR in 330 smokers with COPD (COPD), 658 smokers without COPD (SNC) and 150 nonsmokers (NCNS), the analysis of samples used was χ2 test. Using ELISA, the proteins were evaluated. Multiple comparisons were made by ANOVA. Results: rs243864 (OR: 7.44; 95% CI: 3.62–15.26) and rs11646643 (OR: 1.58; 95% CI: 1.07–2.34) of the MMP-2 gene and rs3918253 (OR: 1.72; 95% CI: 1.08–2.71) of the MMP-9 gene, were associated with the risk of COPD. Serum MMP-2 level in the COPD group was lower compared with SNC (p < 0.05). Serum MMP-9 level was elevated in the COPD group compared with SNC (p < 0.05). Conclusion: Polymorphisms in MMP2 and MMP9 but not in MMP1 and MMP12 are associated with the risk of COPD in the Mexican mestizo population.

Introduction Chronic obstructive pulmonary disease (COPD) is characterized by restricted airflow. The best-documented genetic factor is alpha-1 antitrypsin (AAT). AAT is encoded by the SERPINA1 gene. The PiZ (rs28929474) and PiS (rs17580) variants are believed to cause severe AAT deficiency and are linked to a high risk of developing COPD. This study sought to identify whether genetic polymorphisms rs28929474 and rs17580 are associated with COPD susceptibility and lung function values in a Mexican mestizo population. Methods In this study, 558 smokers were included, of whom 279 had COPD and 279 did not (smokers without COPD – SWC). The PiS and PiZ variants were genotyped by allelic discrimination. Independent populations and lung function values were compared using the Kruskal–Wallis test. A bivariate logistic regression analysis was also conducted. Results Stage I and IV COPD patients showed significant differences in the frequencies of both heterozygous genotypes compared to SWC. For PiS, individuals with the heterozygous genotype AT demonstrated a decreased FEV1/FVC ratio compared to subjects with the homozygous genotype AA (P=.037). A significant association was found between the FEV1/FVC ratio and genotype AA for PiS (OR = 0.982, β coefficient = −0.019, 95% CI = 0.966–0.997). Conclusions COPD-causing AAT deficiency risk alleles exist at a very low frequency among Mexican mestizo population. Although they are not directly linked in our study population with disease susceptibility, these risk alleles are associated with poorer lung function measurements. It is important to characterize how often these genetic risk variants occur in other Latin American populations.

Aim: To evaluate the association of three single nucleotide polymorphisms in TNF and one in LTA in Mexican patients with aspirin-exacerbated respiratory disease (AERD) and the correlation of those single nucleotide polymorphisms with serum levels of TNF-α. Patients & methods: Case–control study including 133 patients with AERD, 135 patients with asthma (aspirin-tolerant asthmatics) and 182 healthy subjects. Results: GA genotype of rs1800629 in TNF was found to be associated with the risk of developing AERD (p

In chronic obstructive pulmonary disease (COPD) are two clinical phenotypes, emphysema and chronic bronchitis. Phenotypes share clinical symptoms such as dyspnea and bronchial obstruction to air fl ow and an increase of innate immune cells (macrophages and neu-trophils), the release of multiple in fl ammatory mediators (chemokines, cytokines, and growth factors), oxidative stress, increased extracellular matrix metalloproteinases (MMPs) in the airways and lung. Disease progression is associated with the presence of chronic in fl ammation and increased proteolytic activity of enzymes such as MMPs resulting in the degradation of elastin and collagen fi bers in the walls of the alveoli and the lung’s extracellular matrix. Of particular interest for this review was to describe the role of MMPs, their participati on in the development of COPD, both in the extracellular matrix destruction and abnormal lung remodeling damaged. Also mentioned genetic association studies of polymorphisms in MMPs type SNP in Caucasian populations such as the development and progression of COPD, and the importance of carrying out studies in Mexican mestizo population. The role of MMPs has also been known through animal models and knockout mic e MMPs exposed to cigarette smoke. All these studies implicate MMPs as key mediators in the pathogenesis of COPD. Finally, the study o f MMPs base allow for future therapies, potential therapeutic targets and disease treatments.

SummaryHypersensitivity Pneumonitis (HP) is a lung inflammatory disorder caused by inhalation of organic particles by a susceptible host. Since only a small proportion of individuals exposed to HP-related antigens develop the disease, a genetic predisposition is largely suspected. However, studies regarding genetic susceptibility in this disease are scanty. We have previously found evidence supporting increased risk associated to the major histocompatibility complex (MHC) in sporadic HP. In the present study, we conducted a family-based research that includes nine multicase families with at least two related HP patients (RHP). We evaluated 19 RHP individuals, 25 additional healthy first-degree relatives (REA) and 246 healthy unrelated individuals (HUI). HLA class II typing (DRB1/3/4/5, DQA1, DQB1, DPA1, DPB1, DMA and DMB), and -863, -308 and -238 polymorphisms in the promoter region of TNF-α were performed by PCR based methods. We identified an increased frequency of HLA-DRB1*04:07, DRB1*04:05, DRB1*11:01 and DRB1*13:01 alleles in RHP individuals compared to healthy controls (p