摘要
目的探讨血管紧张素转化酶（ACE）插入／缺失基因多态性、基质金属蛋白酶-1（MMP-1）-1607位点1G／2G基因多态性与河北地区汉族人群特发性肺纤维化（IPF）患病风险的关系。方法选取2009年11月至2011年5月河北医科大学第二医院呼吸内科临床确诊为IPF的住院患者84例（IPF组）及同期体检中心健康汉族人群100名（对照组），分别应用聚合酶链反应（PCR）技术和聚合酶链反应-限制性片段长度多态性（PCR—RFLP）技术检测ACE插入／缺失基因多态性以及MMP-1＋16071G／2G基因多态性基因型分布，并采用完全随机法抽取样本测序验证，同时采用竞争放射免疫分析法测定血管紧张素Ⅱ（AngⅡ）含量，酶联免疫反应（ELISA）技术测定血清MMP-1、基质金属蛋白酶抑制剂-1（TIMP-1）浓度变化。结果（1）IPF组ACE插入／缺失基因多态性的DD基因型分布频率为47．6％（40／84），高于对照组的24％（24／100），差异有统计学意义（χ2=11．227，P〈0．05），IPF组D等位基因分布频率为61．3％（103／168），高于对照组的50．5％（101／200），差异有统计学意义（χ2=4．318，P〈0．05）；ACE插入／缺失基因多态性在IPF患者不同性别基因型及等位基因频率分布差异无统计学意义（χ2值分别为1．069和0．030，P〉0．05）；不同年龄段基因型及等位基因差异无统计学意义（χ2值分别为0．456及0．511，P〉0．05）。IPF组及对照组血浆AngⅡ水平均以DD基因型最高，D1次之，Ⅱ最低。IPF组各基因型血浆AngⅡ水平均高于对照组（均P〈0．05）。MMP-1-1607位点1G／2G基因多态性各基因型及等位基因分布频率两组间比较差异无统计学意义（χ2值分别为0．94和0．001，均P〉0．05）。（2）IPF组血浆AngⅡ含量、血清MMP-1和TIMP-1蛋白浓度、MMP-1／TIMP-1比值均高于对照组，差异有统计学意义（均P〈0．05）。结论（1）ACE插入／缺失基因多态性与IPF发病可能存在相关性，血浆AngⅡ浓度既受ACE插入／缺失基因多态性影响也受环境因素影响。MMP-1—1607位点1G／2G基因多态性可能与IPF发病不相关。（2）IPF患者血浆中AngⅡ、血清中MMP-1和TIMP-1浓度、MMP-1／TIMP-1比值的升高与IPF发病可能存在相关性。
Objective To investigate the correlation between angiotensin converting enzyme（ACE） and matrix metallo proteinase（ MMP）-1 gene polymorphisms and the risk of idiopathic pulmonary fibrosis （IPF） in a Hart Chinese population from Hebei Province. Methods Eighty-four IPF patients and 100 controls were enrolled from the Second Hospital of Hebei Medical University. Polymerase chain reaction（PCR） and polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP） were used to detect ACE gene insertion/deletion （I/D） polymorphism and MMP-1 polymorphism respectively. The MMP-1 polymorphism was genotyped by DNA sequence analysis. Radioimmunoassay and ELISA were used to analyzed AngII, MMP-1 and TIMP-1 levels in IPF patients and healthy controls. Results There was a significant difference between the 2 groups in allele and genotype frequency distribution of ACE Insertion/Deletion polymorphism ; frequency distribution of DD genotype and D allele of IPF patients were higher than those of the healthy control group （χ2 = 11. 227, 4. 318, P 〈0. 05）. There was no difference from different genders and ages on allele and genotype frequency distribution of ACE Insertion/Deletion polymorphism. （χ2 = 0. 03 - 1. 069, P 〉 0. 05 ）. There was no significant difference between the 2 groups in geuotype and allele frequency distribution of MMP-1 1G/2G polymorphism （χ2 = 0. 94 and 0. 001, P 〉 0. 05 ）. The AngⅡ levels from DD genotype of both IPF patients and healthy controls were the highest, followed by the DI genotype and the Ⅱ genotype. The AngⅡ level of any genotype for ACE Insertion/Deletion polymorphism in the IPF group was higher than that in the healthy control group（ all P 〈 0. 05 ）. The serum level of AngH, MMP-1 and TIMP-1, as well as MMP-1/TIMP-1 ratio in the IPF group were higher than those in the healthy control group（ all P 〈 0. 05 ）. Conclusions The ACE polymorphism might be associated with IPF, and the serum level of AngⅡ was affected not only by the genetic background of ACE insertion/deletion polymorphism but also the environmental factors. The MMP-1 1G/2G polymorphism might be weakly associated with IPF.
出处
《中华结核和呼吸杂志》
CAS
CSCD
北大核心
2013年第1期38-43,共6页
Chinese Journal of Tuberculosis and Respiratory Diseases
基金
河北省科技厅课题（002061123D）
关键词
肺纤维化
基质金属蛋白酶1
多态性
单核苷酸
Pulomonary fibrosis
Matrix metalloproteinase 1
Polymorphism, single nucleotide
