MMP2、MMP3及TIMP2基因多态性与慢性阻塞性肺疾病易感性的研究
发布时间：2018-11-19 08:59
【摘要】：目的： 慢性阻塞性肺疾病（chronic obstructive pulmonary disease，COPD）是一种具有气流受限特征的肺部慢性疾病，炎症、气道重建以及肺实质的损伤是其主要特征。基质金属蛋白酶(matrix metalloproteinases, MMPs)与基质金属蛋白酶组织抑制因子(tissue inhibitor of metalloproteinase, TIMPs)在正常机体中保持动态平衡，维持着机体正常的生理状态。当某些酶活性改变导致MMPs/TIMPs处于不平衡状态时，可能会引起疾病的发生。近年来MMPs/TIMPs平衡失调与COPD的关系得到了广泛关注，本研究通过对中国江西189例汉族人MMP2、MMP3及TIMP2基因多态性与COPD易感性的相关研究，以期能筛选出COPD的易感基因，从而从探索COPD遗传机制方面出发，为进一步研究COPD的早期预防、诊断和治疗提供理论依据。 方法： 采用病例-对照的研究方法，收集我院门诊或住院已经确诊的江西籍汉族COPD患者109例，经问卷调查了解患者病史、吸烟史，并行体检、X线胸片检查、基础肺功能和舒张实验测定以了解患者肺部情况。收集体检科筛选出的80名健康体检者作为健康对照组。两组均否认有间质性肺疾病、肺结核、哮喘等呼吸系统疾病及心脏病病史。所有研究对象均空腹抽取外周血，提取全血细胞DNA，用聚合酶链反应限制性片段长度多态性方法检测两组研究对象MMP2-735C/T、MMP3-11715A/6A和TIMP2+853A/G各位点等位基因和基因型。各组间年龄、肺功能等的比较采用t检验，基因型和等位基因频率的比较采用χ~2检验，用Logistic回归计算OR值及95%CI。 结果： MMP2和MMP3各位点基因型及等位基因频率分布在COPD组和对照组间差异均无统计学意义（MMP2的χ~2值分别为1.95和0.47， MMP3的χ~2值分别为1.05和0.72，均P0.05）；但MMP3-11715A/6A位点的6A/6A基因型在Ⅲ-Ⅳ级COPD患者中出现频率更高，与重度、极重度COPD的发病风险相关，OR值为2.677（1.177~6.088）；TIMP2+853A/G位点基因型及等位基因频率分布在COPD组和对照组间差异有统计学意义（χ~2值分别为6.77和6.31，均P0.05），，与A/A+A/G基因型相比，G/G基因型能增加COPD的发病风险，OR值为2.250（1.215~4.167），携带G等位基因也与COPD的发病风险相关，OR值为1.944（1.151~3.284）。 结论： 1、TIMP2+853A/G位点基因多态性可能与江西汉族人COPD易感性相关，携带G等位基因与COPD的发病风险相关，可能是COPD的易感基因。 2、MMP3-11715A/6A位点6A/6A基因型可能与重度、极重度COPD的发病风险相关联。 3、MMP2-735C/T位点基因多态性与江西汉族人COPD易感性无明显相关。
[Abstract]:Objective: chronic obstructive pulmonary disease (chronic obstructive pulmonary disease,COPD) is a kind of chronic pulmonary disease with airflow limitation. Inflammation, airway remodeling and lung parenchyma injury are the main characteristics of chronic obstructive pulmonary disease (chronic obstructive pulmonary disease,COPD). Matrix metalloproteinase (matrix metalloproteinases, MMPs) and tissue inhibitor of matrix metalloproteinase (tissue inhibitor of metalloproteinase, TIMPs) maintain dynamic balance and maintain normal physiological state in normal organism. When some enzyme activity changes lead to MMPs/TIMPs in an unbalanced state, may cause disease. In recent years, the relationship between MMPs/TIMPs imbalance and COPD has received extensive attention. This study studied the relationship between MMP2,MMP3 and TIMP2 gene polymorphisms and COPD susceptibility in 189 Han Chinese in Jiangxi, China, in order to screen the susceptible genes of COPD. From the aspect of exploring the genetic mechanism of COPD, it provides theoretical basis for further study on early prevention, diagnosis and treatment of COPD. Methods: a case-control study was used to collect 109 COPD patients from Jiangxi Han nationality who had been diagnosed in outpatient or inpatient department of our hospital. The patients' history of disease, smoking history, physical examination and chest X-ray examination were investigated by questionnaire. Basic pulmonary function and diastolic tests were performed to understand the pulmonary status of the patients. A total of 80 healthy persons selected by the Department of physical examination were selected as the healthy control group. Both groups denied a history of interstitial lung disease, pulmonary tuberculosis, asthma and heart disease. Peripheral blood was extracted from all subjects on an empty stomach and whole blood cell DNA, was extracted to detect MMP2-735C/T, by polymerase chain reaction restriction fragment length polymorphism (PCR). Alleles and genotypes of MMP3-11715A/6A and TIMP2 853A/G. T test was used to compare age and lung function, 蠂 ~ 2 test was used to compare genotype and allele frequency, and OR value and 95 CI were calculated by Logistic regression. Results: there was no significant difference in genotype and allele frequency distribution between COPD group and control group (蠂 ~ 2 value of MMP2 was 1.95 and 0.47, 蠂 ~ 2 value of MMP3 was 1.05 and 0.72 respectively, P0.05). However, the frequency of 6A/6A genotypes at MMP3-11715A/6A locus was higher in COPD patients with grade 鈪
本文编号：2341797
[Abstract]:Objective: chronic obstructive pulmonary disease (chronic obstructive pulmonary disease,COPD) is a kind of chronic pulmonary disease with airflow limitation. Inflammation, airway remodeling and lung parenchyma injury are the main characteristics of chronic obstructive pulmonary disease (chronic obstructive pulmonary disease,COPD). Matrix metalloproteinase (matrix metalloproteinases, MMPs) and tissue inhibitor of matrix metalloproteinase (tissue inhibitor of metalloproteinase, TIMPs) maintain dynamic balance and maintain normal physiological state in normal organism. When some enzyme activity changes lead to MMPs/TIMPs in an unbalanced state, may cause disease. In recent years, the relationship between MMPs/TIMPs imbalance and COPD has received extensive attention. This study studied the relationship between MMP2,MMP3 and TIMP2 gene polymorphisms and COPD susceptibility in 189 Han Chinese in Jiangxi, China, in order to screen the susceptible genes of COPD. From the aspect of exploring the genetic mechanism of COPD, it provides theoretical basis for further study on early prevention, diagnosis and treatment of COPD. Methods: a case-control study was used to collect 109 COPD patients from Jiangxi Han nationality who had been diagnosed in outpatient or inpatient department of our hospital. The patients' history of disease, smoking history, physical examination and chest X-ray examination were investigated by questionnaire. Basic pulmonary function and diastolic tests were performed to understand the pulmonary status of the patients. A total of 80 healthy persons selected by the Department of physical examination were selected as the healthy control group. Both groups denied a history of interstitial lung disease, pulmonary tuberculosis, asthma and heart disease. Peripheral blood was extracted from all subjects on an empty stomach and whole blood cell DNA, was extracted to detect MMP2-735C/T, by polymerase chain reaction restriction fragment length polymorphism (PCR). Alleles and genotypes of MMP3-11715A/6A and TIMP2 853A/G. T test was used to compare age and lung function, 蠂 ~ 2 test was used to compare genotype and allele frequency, and OR value and 95 CI were calculated by Logistic regression. Results: there was no significant difference in genotype and allele frequency distribution between COPD group and control group (蠂 ~ 2 value of MMP2 was 1.95 and 0.47, 蠂 ~ 2 value of MMP3 was 1.05 and 0.72 respectively, P0.05). However, the frequency of 6A/6A genotypes at MMP3-11715A/6A locus was higher in COPD patients with grade 鈪
本文编号：2341797
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