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基质金属蛋白酶-9(MMP-9)1562C>T基因多态性与糖皮质激素治疗特发性肺纤维化患者的疗效

MMP-9 1562C>T Gene Polymorphism and Efficacy of Glucocorticoid Therapy in Idiopathic Pulmonary Fibrosis Patients.

作者信息

Zhang Hai-Tao, Fang Shen-Cun, Wang Cai-Ying, Wang Wei, Wu Jing, Wang Chun, Xu Bin, Zhang Ying-Ming

机构信息

Nine Department of Respiratory Medicine, Nanjing Chest Hospital , Nanjing, 210029, People's Republic of China .

出版信息

Genet Test Mol Biomarkers. 2015 Nov;19(11):591-7. doi: 10.1089/gtmb.2015.0057. Epub 2015 Sep 24.

Abstract

OBJECTIVE

To investigate the relationship between matrix metalloproteinase 9 (MMP-9) gene polymorphism and the efficacy of glucocorticoid therapy in idiopathic pulmonary fibrosis (IPF) patients.

METHODS

We conducted a case-control study. Between January 2013 and September 2014, 115 patients at the Nine Department of Respiratory Medicine, Nanjing Chest Hospital, diagnosed with IPF were enrolled to be the IPF group and 100 healthy subjects were enrolled to be the control group. Prednisone was used to treat IPF patients. Polymerase chain reaction-restriction fragment length polymorphism was used to identify MMP-9 1562C> T polymorphism. The Sandwich enzyme-linked immunosorbent assay was used to measure the serum level of MMP-9 and tissue inhibitor of metalloproteinases 1 (TIMP-1) in the IPF patients before and after the glucocorticoid treatment.

RESULTS

The frequencies of the TT genotype and the T allele of MMP-9 1562C> T gene were found significantly higher in the IPF group compared with the control group (both p < 0.05). Serum levels of MMP-9 and TIMP-1 in IPF patients in each of the three genotype groups before glucocorticoid treatment were significantly higher than those in the control group (all p < 0.05). After the glucocorticoid treatment, MMP-9 and TIMP-1 levels decreased significantly compared with the levels before the glucocorticoid treatment in the IPF patients in each genotype group (all p < 0.05), but were still higher than those in the control group (all p < 0.05). The proportion of "remarkable effect" in the IPF patients of the CC genotype group was significantly higher than that in the other two genotype groups, while the rate of adverse reactions of the CC group was significantly lower than the other two groups (all p < 0.05).

CONCLUSION

MMP-9 gene 1562C> T polymorphism may affect the efficacy of the glucocorticoid therapy for IPF and may be a predictor of IPF treatment outcome.

摘要

目的

探讨基质金属蛋白酶9(MMP-9)基因多态性与特发性肺纤维化(IPF)患者糖皮质激素治疗疗效之间的关系。

方法

我们进行了一项病例对照研究。2013年1月至2014年9月,南京胸科医院呼吸内科九病区诊断为IPF的115例患者纳入IPF组,100例健康受试者纳入对照组。采用泼尼松治疗IPF患者。采用聚合酶链反应-限制性片段长度多态性方法鉴定MMP-9 1562C>T多态性。采用夹心酶联免疫吸附试验检测IPF患者糖皮质激素治疗前后血清MMP-9和金属蛋白酶组织抑制剂1(TIMP-1)水平。

结果

与对照组相比,IPF组MMP-9 1562C>T基因的TT基因型和T等位基因频率显著更高(均p<0.05)。糖皮质激素治疗前,三个基因型组中IPF患者的血清MMP-9和TIMP-1水平均显著高于对照组(均p<0.05)。糖皮质激素治疗后,各基因型组IPF患者的MMP-9和TIMP-1水平与糖皮质激素治疗前相比均显著降低(均p<0.05),但仍高于对照组(均p<0.05)。CC基因型组IPF患者“显著疗效”的比例显著高于其他两个基因型组,而CC组的不良反应发生率显著低于其他两组(均p<0.05)。

结论

MMP-9基因1562C>T多态性可能影响IPF患者糖皮质激素治疗的疗效,可能是IPF治疗结局的一个预测指标。

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