RESUMO
INTRODUCTION: 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. METHODS: 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). RESULTS: An analysis using the codominant model showed an association between rs1818879 in IL6 and susceptibility to COPD (GA ORâ¯=â¯1.1, AA ORâ¯=â¯1.77; pâ¯<â¯0.01), as well as an association between rs25882 in CSF2 and a greater severity of the disease (TC ORâ¯=â¯1.84, CC ORâ¯=â¯3.62; pâ¯<â¯0.01). No association was found between the presence of certain alleles in the SNPs and the plasma levels of the corresponding proteins. CONCLUSIONS: 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.
Assuntos
Citocinas/genética , Inflamação/genética , Polimorfismo de Nucleotídeo Único/genética , Doença Pulmonar Obstrutiva Crônica/genética , Idoso , Alelos , Proteínas Sanguíneas/genética , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença/genética , Genótipo , Humanos , Interleucina-1beta/genética , Interleucina-6/genética , Masculino , Pessoa de Meia-IdadeRESUMO
Asthma and chronic obstructive pulmonary disease (COPD) are widely documented diseases with an inflammatory component. Asthma is a heterogeneous disorder of the airways that involves chronic inflammation, decline of the airway function and tissue remodeling. Chronic obstructive pulmonary disease is a preventable and treatable disease, which is characterized by persistent limited airflow, and is usually progressive with an increased inflammatory response in the airways. The inflammatory response is evoked by the stimulus of noxious particles and gases. Inflammation is a natural process in response to injury, but in asthma and COPD patients it occurs as an abnormal immune response to pathogenic stimuli which induce chronic inflammation, a key process in the pathogenesis of both diseases. However, the inflammatory process is different in both diseases, and is involved in several release patterns of inflammation mediators. It is not entirely clear whether these proteins are simply markers of the inflammatory process that accompanies a chronic disease or if they play a major role in the pathogenesis of the disease. The main proteins which have been described in these illnesses are: IL-4, IL-6, IL-8, and TNF-α. In addition, polymorphisms have been described in genes encoding these proteins that alter the transcription and susceptibility associated with these diseases. In this review, we will focus on asthma and COPD, and the involvement of these proteins and their genetic polymorphisms.
Assuntos
Asma/patologia , Inflamação/genética , Polimorfismo Genético , Doença Pulmonar Obstrutiva Crônica/patologia , Asma/complicações , Humanos , Inflamação/complicações , Inflamação/imunologia , Inflamação/patologia , Pulmão/patologiaRESUMO
BACKGROUND: The influenza A H1N1/09 pandemic infected a small number of exposed individuals, which suggests the involvement of genetic factors. There are scarce data available on classical HLA class I association with the influenza A H1N1/09 pandemic. METHODS: We analyzed the frequency of classical HLA class I alleles and haplotypes in A H1N1/09 influenza in a case-control study including 138 influenza patients (INF-P) and 225 asymptomatic healthy contacts (INF-C) simultaneously recruited. HLA class I typing was performed by high-resolution sequence-based typing method. RESULTS: Our analysis revealed higher frequency of C∗07:02:01, B∗39:06:02, C∗03:02:01, B∗44:03:01, B∗51:01:05, and B∗73:01 (p < 0.05; OR = 1.84-9.98) and of two haplotypes-A∗68:01:02-C∗07:02:01 (p = 1.05E - 05; OR = 23.99) and B∗35:01:01-C∗07:02.01 (p = 4.15E - 04, OR = 2.15)-in A H1N1/09 influenza subjects. A∗68:01:01 was exclusively present only in the INF-P group (5/138). A decrease in the frequency of C∗03:03:01, A∗11:01:01, B∗39:01:01, A∗24:02:01, C∗03:04:01, B∗51:01:01, and C∗07:01:01 (p < 0.05; OR = 0.12-0.52) and of haplotypes A∗02:01:01-B∗35:01:01-C∗04:01:01, A∗24:02:01-B∗35:01:01, B∗39:01:01-C∗07:02:01, and B∗40:02:01-C∗03:04:01 (p < 0.05; OR = 0.08-0.22) were observed in INF-P group. CONCLUSION: Selective classical HLA class I allele and haplotype combinations predispose individuals towards susceptibility or protection against the influenza A H1N1/09 pandemic. This work has significant implications for accessing population transmission risk for A H1N1/09 or a similar strain breakout in the future.
Assuntos
Genótipo , Antígenos HLA/genética , Antígenos de Histocompatibilidade Classe I/genética , Vírus da Influenza A Subtipo H1N1/fisiologia , Influenza Humana/genética , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Teste de Histocompatibilidade , Humanos , Influenza Humana/epidemiologia , Influenza Humana/mortalidade , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Pandemias , Análise de Sobrevida , Carga ViralRESUMO
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 < 0.05; odds ratio = 2.36) and by dominant model (p < 0.05; odds ratio = 2.51). Furthermore, there was a difference in the serum levels between the aspirin-tolerant asthmatics group and the other groups (p < 0.001). CONCLUSION: The GA genotype of rs1800629 is associated with genetic susceptibility to AERD, but it does not correlate to protein serum levels.
Assuntos
Asma Induzida por Aspirina/genética , Predisposição Genética para Doença , Genótipo , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/genética , Adulto , Asma Induzida por Aspirina/epidemiologia , Asma Induzida por Aspirina/etnologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , México/epidemiologia , México/etnologia , Pessoa de Meia-IdadeRESUMO
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=0.037). A significant association was found between the FEV1/FVC ratio and genotype AA for PiS (OR=0.982, ß 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.