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首页> 外文期刊>COPD: Journal of Chronic Obstructive Pulmonary Disease >IL-8 Gene Variants are Associated with Lung Function Decline and Multidimensional BODE Index in COPD Patients But Not with Disease Susceptibility: A Validation Study
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IL-8 Gene Variants are Associated with Lung Function Decline and Multidimensional BODE Index in COPD Patients But Not with Disease Susceptibility: A Validation Study

机译：一项IL-8基因变异与COPD患者肺功能下降和多维BODE指数相关，但与疾病易感性无关：一项验证研究

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Background and objective: COPD is a leading cause of dead worldwide and tobacco smoking is its major risk factor. IL8 is a proinflammatory chemokine mainly involved in the acute inflammatory reaction. The aim of this study was to test the association of IL-8, CXCR1 and CXCR2 gene variants and COPD susceptibility as part of a replication study and explore the effect of these variations in disease progression. Methods: 9 tagSNPs were genotyped in 728 Caucasian individuals (196 COPD patients, 80 smokers and 452 non-smoking controls). Pulmonary compromise was evaluated using spirometry and clinical parameters at baseline and annually over a 2 years period. We also determined plasma levels of TNF-alpha, IL-6, IL-8 and IL-16 in COPD patients. Results: There was a lack of association between gene variants or haplotypes with predisposition to COPD. No correlation was observed between the polymorphisms and cytokines levels. Interestingly, significant associations were found between carriers of the rs4073A (OR = 3.53, CI 1.34-9.35, p = 0.01), rs2227306C (OR = 5.65, CI 1.75-18.88, p = 0.004) and rs2227307T (OR = 4.52, CI = 1.49-12.82, p = 0.007) alleles in the IL-8 gene and patients who scored higher in the BODE index and showed an important decrease in their FEV1 and FVC during the 2 years follow-up period (p < 0.05). Conclusions: Despite no association was found between the studied genes and COPD susceptibility, three polymorphisms in the IL-8 gene appear to be involved in a worse progression of the disease, with an affectation beyond the pulmonary function and importantly, a reduction in lung function along the follow-up years.
机译：背景和目的：COPD是导致全球死亡的主要原因，吸烟是其主要危险因素。 IL8是主要参与急性炎症反应的促炎趋化因子。这项研究的目的是测试IL-8，CXCR1和CXCR2基因变异与COPD敏感性的关联，作为复制研究的一部分，并探讨这些变异对疾病进展的影响。方法：对728名白人（196名COPD患者，80名吸烟者和452名非吸烟对照）的9种tagSNP进行基因分型。使用肺活量测定法和临床参数在基线和两年内每年评估肺功能损害。我们还确定了COPD患者的血浆TNF-α，IL-6，IL-8和IL-16水平。结果：易患COPD的基因变异或单倍型之间缺乏关联。在多态性和细胞因子水平之间没有观察到相关性。有趣的是，在rs4073A（OR = 3.53，CI 1.34-9.35，p = 0.01），rs2227306C（OR = 5.65，CI 1.75-18.88，p = 0.004）和rs2227307T（OR = 4.52，CI = 1.28-12.82，p = 0.007）等位基因和在BODE指数中得分较高且在2年的随访期内其FEV1和FVC显着降低的患者（p <0.05）。结论：尽管没有发现所研究的基因与COPD易感性相关，但IL-8基因中的三个多态性似乎与疾病的恶化有关，其影响超出肺功能，重要的是肺功能降低后续的几年。

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