Matrix metalloproteinase-2 functional promoter polymorphism G1575A is associated with elevated circulatory MMP-2 levels and increased risk of cardiovascular disease in systemic lupus erythematosus patients
Matrix metalloproteinase-2 functional promoter polymorphism G1575A is associated with elevated circulatory MMP-2 levels and increased risk of cardiovascular disease in systemic lupus erythematosus patients
复制标题
DOI：
10.1177/0961203312436857
复制
发表时间：
2012-05-01
期刊：
影响因子：
2.6
通讯作者：
Pourmotabbed, T.
中科院分区：
文献类型：
--
作者：
Bahrehmand, F.;Vaisi-Raygani, A.;Pourmotabbed, T.
基质金属蛋白酶-2（MMP-2）是一种锌依赖性核酸内切酶，可降解基底膜的主要结构成分IV型胶原。MMP-2功能启动子G1575 A多态性影响MMP-2的循环水平，可能是系统性红斑狼疮（SLE）患者心血管疾病（CVD）的重要遗传决定因素。本研究旨在探讨MMP-2 1575 A等位基因与血清MMP-2、新蝶呤、脂蛋白水平及SLE和CVD的关系，并对109例SLE伴或不伴CVD患者进行病例对照研究（平均年龄，35.6岁）和101名来自伊朗西部人群的性别和年龄匹配的、无关的健康对照（平均年龄，37.1岁）。采用聚合酶链反应（限制性片段长度多态性）PCR-RFLP检测MMP-2 1575 G/A多态性，采用酶联免疫吸附试验（ELISA）、高效液相色谱法（HPLC）和酶法分别检测血清MMP-2、新蝶呤和血脂水平。MMP-2G 1575 A等位基因的存在与SLE和CVD的发生相关（OR分别为1.78，p = 0.029和OR = 3.43，p = 0.025）。SLE患者MMP-2A的表达（G/A + A/A）等位基因MMP-2活性较高（301垂直于166 vs. 194垂直于35.5，p = 0.002），新蝶呤（29.4 +/- 39.4 vs. 7.3 +/- 4.6，p = 0.005）、LDL-C（120 +/- 25.7 vs. 87 +/- 39.3，p = 0.045）和较低的HDL-C（39.6 +/- 11 vs. 45.9 +/- 11.8，p = 0.031）水平。SLE合并CVD患者MMP-2水平与新蝶呤、总胆固醇、TG水平呈正相关，与HDL-C水平呈负相关。MMP-2G 1575 A等位基因可能是SLE的危险因素。该等位基因的携带者具有高水平的MMP-2、新蝶呤、总胆固醇和TG以及低水平的HDL，因此，他们更容易患心脏病。Lupus（2012）21，616-624.
Matrix metalloproteinase-2 (MMP-2) is a zinc dependent endonuclease that degrades type IV collagen, the major structural component of basement membranes. MMP-2 functional promoter polymorphism G1575A affects circulating level of MMP-2 and may be considered an important genetic determinant of cardiovascular disease (CVD) in systemic lupus erythematosus (SLE) patients. In this study, association between MMP-2 1575A allele with serum MMP-2, neopterin and lipid-lipoprotein levels and with SLE and developing CVD was investigated.The present case-control study consisted of 109 SLE patients with and without CVD (mean age, 35.6 years) and 101 gender-and age-matched, unrelated, healthy controls (mean age, 37.1 years) from the population in the west of Iran. MMP-2 1575G/A polymorphism was detected by polymerase chain reaction (restriction fragment length polymorphism) PCR-RFLP, serum MMP-2, neopterin and lipid levels were determined by enzyme-linked immunosorbent assay (ELISA), high-performance liquid chromatography (HPLC) and enzyme assay, respectively. The presence of MMP-2 G1575A allele was found to be associated with SLE and developed CVD (OR 1.78, p = 0.029 and OR = 3.43, p = 0.025, respectively). The SLE patients with MMP-2 A (G/A + A/A) allele had higher MMP-2 activity (301 perpendicular to 166 vs. 194 perpendicular to 35.5, p = 0.002), neopterin (29.4 +/- 39.4 vs. 7.3 +/- 4.6, p = 0.005), LDL-C (120 +/- 25.7 vs. 87 +/- 39.3, p = 0.045) and lower HDL-C (39.6 +/- 11 vs. 45.9 +/- 11.8, p = 0.031) levels than the control subjects. There was a significantly positive correlation between MMP-2 level with neopterin, total cholesterol and TG levels and negative correlation with HDL-C level in SLE patients with CVD. MMP-2 G1575A allele may be a risk factor for SLE. The carriers of this allele have high levels of MMP-2, neopterin, total cholesterol and TG and lower levels of HDL, thus, they are more likely to develop heart disease. Lupus (2012) 21, 616-624.