MMP2、MMP3及TIMP2基因多態(tài)性與慢性阻塞性肺疾病易感性的研究
發(fā)布時(shí)間：2018-11-19 08:59
【摘要】：目的： 慢性阻塞性肺疾病（chronic obstructive pulmonary disease，COPD）是一種具有氣流受限特征的肺部慢性疾病，炎癥、氣道重建以及肺實(shí)質(zhì)的損傷是其主要特征�；|(zhì)金屬蛋白酶(matrix metalloproteinases, MMPs)與基質(zhì)金屬蛋白酶組織抑制因子(tissue inhibitor of metalloproteinase, TIMPs)在正常機(jī)體中保持動(dòng)態(tài)平衡，維持著機(jī)體正常的生理狀態(tài)。當(dāng)某些酶活性改變導(dǎo)致MMPs/TIMPs處于不平衡狀態(tài)時(shí)，可能會(huì)引起疾病的發(fā)生。近年來(lái)MMPs/TIMPs平衡失調(diào)與COPD的關(guān)系得到了廣泛關(guān)注，本研究通過(guò)對(duì)中國(guó)江西189例漢族人MMP2、MMP3及TIMP2基因多態(tài)性與COPD易感性的相關(guān)研究，以期能篩選出COPD的易感基因，從而從探索COPD遺傳機(jī)制方面出發(fā)，為進(jìn)一步研究COPD的早期預(yù)防、診斷和治療提供理論依據(jù)。 方法： 采用病例-對(duì)照的研究方法，收集我院門診或住院已經(jīng)確診的江西籍漢族COPD患者109例，經(jīng)問(wèn)卷調(diào)查了解患者病史、吸煙史，并行體檢、X線胸片檢查、基礎(chǔ)肺功能和舒張實(shí)驗(yàn)測(cè)定以了解患者肺部情況。收集體檢科篩選出的80名健康體檢者作為健康對(duì)照組。兩組均否認(rèn)有間質(zhì)性肺疾病、肺結(jié)核、哮喘等呼吸系統(tǒng)疾病及心臟病病史。所有研究對(duì)象均空腹抽取外周血，提取全血細(xì)胞DNA，用聚合酶鏈反應(yīng)限制性片段長(zhǎng)度多態(tài)性方法檢測(cè)兩組研究對(duì)象MMP2-735C/T、MMP3-11715A/6A和TIMP2+853A/G各位點(diǎn)等位基因和基因型。各組間年齡、肺功能等的比較采用t檢驗(yàn)，基因型和等位基因頻率的比較采用χ~2檢驗(yàn)，用Logistic回歸計(jì)算OR值及95%CI。 結(jié)果： MMP2和MMP3各位點(diǎn)基因型及等位基因頻率分布在COPD組和對(duì)照組間差異均無(wú)統(tǒng)計(jì)學(xué)意義（MMP2的χ~2值分別為1.95和0.47， MMP3的χ~2值分別為1.05和0.72，均P0.05）；但MMP3-11715A/6A位點(diǎn)的6A/6A基因型在Ⅲ-Ⅳ級(jí)COPD患者中出現(xiàn)頻率更高，與重度、極重度COPD的發(fā)病風(fēng)險(xiǎn)相關(guān)，OR值為2.677（1.177~6.088）；TIMP2+853A/G位點(diǎn)基因型及等位基因頻率分布在COPD組和對(duì)照組間差異有統(tǒng)計(jì)學(xué)意義（χ~2值分別為6.77和6.31，均P0.05），，與A/A+A/G基因型相比，G/G基因型能增加COPD的發(fā)病風(fēng)險(xiǎn)，OR值為2.250（1.215~4.167），攜帶G等位基因也與COPD的發(fā)病風(fēng)險(xiǎn)相關(guān)，OR值為1.944（1.151~3.284）。 結(jié)論： 1、TIMP2+853A/G位點(diǎn)基因多態(tài)性可能與江西漢族人COPD易感性相關(guān)，攜帶G等位基因與COPD的發(fā)病風(fēng)險(xiǎn)相關(guān)，可能是COPD的易感基因。 2、MMP3-11715A/6A位點(diǎn)6A/6A基因型可能與重度、極重度COPD的發(fā)病風(fēng)險(xiǎn)相關(guān)聯(lián)。 3、MMP2-735C/T位點(diǎn)基因多態(tài)性與江西漢族人COPD易感性無(wú)明顯相關(guān)。
[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
本文編號(hào)：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
本文編號(hào)：2341797
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