NRF2/KEAP1 通路与抗氧化防御基因多态性与慢性阻塞性肺疾病的相关性。
Associations of the NRF2/KEAP1 pathway and antioxidant defense gene polymorphisms with chronic obstructive pulmonary disease.
机构信息
Institute of Biochemistry and Genetics - Subdivision of the Ufa Federal Research Centre of the Russian Academy of Sciences (IBG UFRC RAS), Pr. Oktybry 71, Ufa 450054, Russian Federation.
Institute of Biochemistry and Genetics - Subdivision of the Ufa Federal Research Centre of the Russian Academy of Sciences (IBG UFRC RAS), Pr. Oktybry 71, Ufa 450054, Russian Federation.
出版信息
Gene. 2019 Apr 15;692:102-112. doi: 10.1016/j.gene.2018.12.061. Epub 2019 Jan 12.
BACKGROUND AND OBJECTIVE
Chronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease of the respiratory system affecting primarily distal respiratory pathways and lung parenchyma. This work was designed as a case-control study aimed at investigating the association of the NRF2/KEAP1 signaling system, and antioxidant defense gene polymorphisms with COPD in population from Russia.
METHODS
Ten SNPs: NFE2L2 (rs35652124), KEAP1 (rs1048290), MPO (rs2333227), PRNP (rs1799990), PTGR1 (rs2273788), HSPA1A (rs1008438), TXNRD2 (rs1139793), GSR (rs1002149), SIRT2 (rs10410544), and PTGS1 (rs1330344) were genotyped by the real-time polymerase chain reaction (TaqMan assays) in a case-control study (425 COPD patients and 457 controls, from the same region of Russia, representatives of Tatar population). Logistic regression was used to detect the association of SNPs in different models. Linear regression analyses were performed to estimate the relationship between SNPs and lung function parameters and smoking pack-years.
THE RESULTS
In our population, a significant associations of KEAP1 (rs1048290) (P = 0.0015, OR = 0.72 in additive model), HSPA1A (rs1008438) (P = 0.006, OR = 2.26 in recessive model), GSR (rs1002149) (P = 0.037, OR = 1.31 in additive model) with COPD were revealed. NFE2L2 (rs35652124), PRNP (rs1799990), and HSPA1A (rs1008438) were significantly associated with COPD only in smokers. In nonsmokers, significant association was established for GSR (rs1002149). KEAP1 (rs1048290) was associated with COPD in both groups. The relationship between KEAP1 (rs1048290), NFE2L2 (rs35652124), and HSPA1A (rs1008438) and smoking pack-years was found (P = 0.005, P = 0.0028, P = 0.015). A significant genotype-dependent variation of forced vital capacity and forced expiratory volume in 1 s was observed for SIRT2 (rs10410544) (P = 0.04), NFE2L2 (rs35652124) (P = 0.028), and PRNP (rs1799990) (P = 0.044).
背景与目的
慢性阻塞性肺疾病（COPD）是一种复杂的慢性呼吸系统炎症性疾病，主要影响远端呼吸道和肺实质。本研究旨在探讨 NRF2/KEAP1 信号系统和抗氧化防御基因多态性与俄罗斯人群 COPD 的相关性，为此我们进行了病例对照研究。
方法
在病例对照研究（425 例 COPD 患者和 457 例对照，来自俄罗斯同一地区，代表鞑靼人群）中，使用实时聚合酶链反应（TaqMan 检测法）对 10 个 SNP（NFE2L2(rs35652124)、KEAP1(rs1048290)、MPO(rs2333227)、PRNP(rs1799990)、PTGR1(rs2273788)、HSPA1A(rs1008438)、TXNRD2(rs1139793)、GSR(rs1002149)、SIRT2(rs10410544)和 PTGS1(rs1330344)）进行基因分型。采用逻辑回归在不同模型中检测 SNP 的相关性。采用线性回归分析来评估 SNP 与肺功能参数和吸烟包年数之间的关系。
结果
在我们的人群中，KEAP1(rs1048290)（P=0.0015，加性模型中 OR=0.72）、HSPA1A(rs1008438)（P=0.006，隐性模型中 OR=2.26）和 GSR(rs1002149)（P=0.037，加性模型中 OR=1.31）与 COPD 存在显著相关性。NFE2L2(rs35652124)、PRNP(rs1799990)和 HSPA1A(rs1008438)仅在吸烟者中与 COPD 显著相关。在不吸烟者中，GSR(rs1002149)与 COPD 存在显著相关性。KEAP1(rs1048290)在两组中均与 COPD 相关。还发现了 KEAP1(rs1048290)、NFE2L2(rs35652124)和 HSPA1A(rs1008438)与吸烟包年数之间的关系（P=0.005、P=0.0028、P=0.015）。SIRT2(rs10410544)（P=0.04）、NFE2L2(rs35652124)（P=0.028）和 PRNP(rs1799990)（P=0.044）的基因型依赖性变化与用力肺活量和 1 秒用力呼气量有显著相关性。
请注意，由于你提供的文本没有提供 SNP 对应的中文名称，因此我无法将其准确翻译为中文。如果你能提供更多的 SNP 信息，我将尽力为你提供更准确的翻译。
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