烟草烟雾代谢与抗氧化应激通路关键分子基因多态性与中国汉族人群慢性阻塞性肺疾病遗传易感性的关联及机制研究

Chronic obstructive pulmonary disease (COPD), including chronic pulmonary emphysema and chronic bronchitis, is one of the leading causes of morbidity and mortality worldwide. It is characterized by a partially reversible airflow limitation, which is usually progressive and associated with abnormal inflammatory responses of the lungs when exposed to noxious particles or gases..The pathogenesis of COPD is complex and impacted by the interaction between genetic susceptibility and environmental exposure..Smoking is the principal environmental risk factor for developing COPD and several studies have reported that the gene EGLN2 and CYP2E1 is related to tobacco smoke metabolism.NRF2/KEAP1-BACH1-PRDX6 is an important antioxidant stress pathway, which can detoxify reactive oxygen species (ROS) generated from tobacco smoke or endogenous ROS generated from inflammatory cells indirectly. NRF2 is a transcription factor upregulates the expression of antioxidant gene involved in the pathogenesis of COPD. .This study aimed to explore the association and mechanism of tobacco smoke metabolism related genes EGLN2 and CYP2E1 and the anti-oxidative stress pathways critical molecular NRF2/KEAP1-BACH1-PRDX6 gene polymorphism with COPD in a Chinese Han population.And investigated the relationship between the gene polymorphism and the severity of COPD as well as emphysema severity.We provided a new theoretical basis for understanding the pathogenesis of COPD and may benefit COPD screening of early prevention,diagnosed and treatment.

慢性阻塞性肺病是一种以气流受限为特征的慢性气道疾病，气流受限不完全可逆，呈进行性发展。其发病机制复杂，与遗传因素及环境因素相互作用有关。.吸烟是已被证实的慢阻肺最主要的危险因素，近年来研究发现EGLN2、CYP2E1与烟草烟雾代谢有关。NRF2/KEAP1-BACH1-PRDX6是重要的抗氧化应激通路之一,能解毒烟草烟雾直接或间接产生的活性氧簇，转录因子NRF2/BACH1竞争反向调节抗氧化基因表达参与慢阻肺的发病过程。.本研究利用病例-对照研究方法探讨烟草烟雾代谢相关基因EGLN2、CYP2E1以及抗氧化应激通路关键分子NRF2/KEAP1-BACH1-PRDX6基因多态性与中国汉族人群COPD患者遗传易感性、疾病严重程度和肺气肿程度是否具有相关性，从而找出影响COPD发生的风险基因,为研究COPD的发病机制提供相关理论基础，为疾病的早期诊断、个性化预防和治疗提供科学依据。

慢性阻塞性肺病是一种以气流受限为特征的慢性气道疾病，气流受限不完全可逆，呈进行性发展。其发病机制复杂，与遗传因素及环境因素相互作用有关。.吸烟是已被证实的慢阻肺最主要的危险因素，近年来研究发现EGLN2、CYP2E1与烟草烟雾代谢有关。NRF2/KEAP1-BACH1-PRDX6是重要的抗氧化应激通路之一,能解毒烟草烟雾直接或间接产生的活性氧簇，转录因子NRF2/BACH1竞争反向调节抗氧化基因表达参与慢阻肺的发病过程。.本研究利用病例-对照研究方法探讨烟草烟雾代谢相关基因EGLN2、CYP2E1以及抗氧化应激通路关键分子NRF2/KEAP1-BACH1-PRDX6基因多态性与中国汉族人群COPD患者遗传易感性、疾病严重程度和肺气肿程度之间的关联性研究，发现：1、EGLN2和PRDX6基因多态性与中国汉族人群慢阻肺易感性相关。其中EGLN2基因多态性可能是通过与吸烟相互作用参与慢阻肺的发生发展。2、BACH1基因多态性与中国汉族人群慢阻肺易感性不相关，但与慢阻肺严重程度相关。3、分析候选基因多态性与慢阻肺患者临床参数的相关性，发现CYP2E1、BACH1、EGLN2 基因多态性与肺气肿程度相关，PRDX6和CYP2E1基因多态性与慢阻肺患者吸烟行为相关，PRDX6、NRF2、BACH1 基因多态性与肺功能指标相关。4、这些研究结果提示基因多态性与疾病关联研究中需强调准确的临床表型，同一基因不同SNP位点可能与疾病的不同表型具有相关性。该项研究为慢阻肺的发病机制研究带来了崭新的视角，为疾病的个性化预防和诊疗提供依据。