慢性阻塞性肺疾病发生及治疗反应差异相关基因的研究进展

Research progress on genes related to occurrence and differences in treatment response of chronic obstructive pulmonary disease

慢性阻塞性肺疾病(COPD)是一种遗传和环境等多种因素共同作用所致的肺部疾病,以不可逆的气流受限为主要特征。近年来,COPD遗传学相关研究又有了一些新的发现,如丝氨酸蛋白酶抑制剂A1基因的rs8004738位点、转化生长因子β1基因的rs1982073位点、非受体型蛋白酪氨酸磷酸酶6基因、端粒酶逆转录酶基因及基质金属蛋白酶基因家族均与COPD显著相关;在此基础上还发现了多个与COPD治疗反应差异有关的基因,如钾内向整流通道J亚家族成员2基因,皮质类固醇受体基因及糖皮质激素诱导转录因子1基因。这些新发现的基因及位点多态性为COPD的发病机制提供了新见解,为寻找COPD诊疗新靶点,建立COPD患者不同表型的分型依据及预测模型提供了方向,推动了个体化治疗的发展。

Chronic obstructive pulmonary disease(COPD)is a lung disease caused by a combination of genetic and environmental factors,and is characterized by irreversible airflow limitations.In recent years,new discoveries have been made in COPD genetics-related studies,such as the rs8004738 locus of serpin family A member 1,the rs1982073 locus of transforming growth factorβ1,protein tyrosine phosphatase non-receptor type 6,telomerase reverse tranasecriptase gene,and matrix metalloproteinases have all been significantly associated with COPD;on this basis,several genes associated with differences in treatment response of COPD were also identified,such as potassium inwardly rectifying channel subfamily J member 2,nuclear receptor subfamily 3 group C member 1,and glucocorticoid inducible transcription factor 1.These newly identified genes and loci provide new insights into the pathogenesis of COPD,provide directions for finding new targets for the diagnosis and treatment of COPD,establish the basis for typing and prediction models for different phenotypes of COPD patients and promote the development of individualized therapy.