RESUMO
BACKGROUND: Genome-wide association studies (GWAS) have accelerated our understanding of the genetic underpinnings of chronic obstructive pulmonary disease (COPD); however, GWAS populations have typically consisted of European descent, with â¼1% of Latin American ancestry. OBJECTIVE: To overcome this limitation, we conducted a GWAS in a rural Chilean population with increased COPD risk to investigate genetic variation of COPD risk in this understudied minority population. METHOD: We carried out a case-control study of 214 COPD patients (defined by the GOLD criteria) and 193 healthy controls in Talca, Chile. DNA was extracted from venous blood and genotyped on the Illumina Global Screening Array (n = 754,159 markers). After exclusion based on Hardy-Weinberg equilibrium (p ≤ 0.001), call rates (<95%), and minor allele frequencies (<0.5%) in controls, 455,564 markers were available for logistic regression. RESULTS: PRDM15 rs1054761 C allele (p = 2.22 × 10-7) was associated with decreased COPD risk. Three PRDM15 SNPs located on chromosome 21 were significantly associated with COPD risk (p < 10-6). Two of these SNPs, rs1054761 and rs4075967, were located on a noncoding transcript variant region of the gene. CONCLUSION: PRDM15 overexpression may play a role in the B-cell dysregulation in COPD pathogenesis. To the best of our knowledge, the association between PRDM15 and COPD risk was not previously found in GWAS studies in largely European populations, highlighting the importance of investigating novel variants associated with COPD risk among ethnically diverse populations.
Assuntos
Proteínas de Ligação a DNA/genética , Doença Pulmonar Obstrutiva Crônica/genética , Fatores de Transcrição/genética , Idoso , Poluição do Ar em Ambientes Fechados/estatística & dados numéricos , Biomassa , Estudos de Casos e Controles , Chile/epidemiologia , Feminino , Volume Expiratório Forçado , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Modelos Logísticos , Masculino , Polimorfismo de Nucleotídeo Único , Capacidade de Difusão Pulmonar , População Rural , Índice de Gravidade de Doença , Fumar/epidemiologia , Capacidade VitalRESUMO
Approximately 3 million people in the world die every year as a consequence of COPD, which is associated with an abnormal inflammatory response of the lung to noxious particles and gases. This inflammatory pattern causes pathological changes leading to a narrowing of small airways and destruction of lung parenchyma, also known as emphysema. Classically, these changes were associated to macrophages and neutrophils, although T CD8+ lymphocytes were latter added to the equation to explain the origin of emphysematous lesions. However, in recent years, multiple evidences have arisen indicating that inflammatory response in COPD is much more complex. These findings point to a key role for mast cells, dendritic cells, T CD4+ and B cells. The aim of this article is to review such evidence and report what is known so far about those cells involved in the inflammatory response in COPD.
Assuntos
Inflamação/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Linfócitos B/fisiologia , Linfócitos T CD4-Positivos/fisiologia , Linfócitos T CD8-Positivos/fisiologia , Células Dendríticas/fisiologia , Humanos , Macrófagos Alveolares/fisiologia , Mastócitos/fisiologia , Neutrófilos/fisiologiaRESUMO
Approximately 3 million people in the world die every year as a consequence of COPD, which is associated with an abnormal inflammatory response of the lung to noxious particles and gases. This inflammatory pattern causes pathological changes leading to a narrowing of small airways and destruction of lung parenchyma, also known as emphysema. Classically, these changes were associated to macrophages and neutrophils, although T CD8+ lymphocytes were latter added to the equation to explain the origin of emphysematous lesions. However, in recent years, multiple evidences have arisen indicating that inflammatory response in COPD is much more complex. These findings point to a key role for mast cells, dendritic cells, T CD4+ and B cells. The aim of this article is to review such evidence and report what is known so far about those cells involved in the inflammatory response in COPD.