Open AccessMMP-2 and MMP-9 gene polymorphisms act as biological indicators for ulinastatin efficacy in patients with severe acute pancreatitis
Author(s) -
Lan Ling,
Yan Li,
Hong Li,
Wen Li,
Hongbo Zhang
Publication year - 2019
Publication title -
medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 148
eISSN - 1536-5964
pISSN - 0025-7974
DOI - 10.1097/md.0000000000015831
Subject(s) - ulinastatin , medicine , genotype , gastroenterology , pancreatitis , multifactor dimensionality reduction , gene , single nucleotide polymorphism , genetics , biology
Background: Severe acute pancreatitis (SAP) is a severe form of inflammatory disease with a high mortality rate. Ulinastatin, as a urinary trypsin inhibitor (UTI), is a glycoprotein playing a critical role in SAP. Consequently, we identified the hypothesis that both matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) gene polymorphisms might promote the efficacy of ulinastatin in SAP. Methods: A total of 235 patients with SAP were treated by intravenous drip of ulinastatin for the duration of 10 days. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed for testing the distribution of genotypes and alleles frequency of MMP-2 and MMP-9 gene polymorphisms, and analyzing association of MMP-2 rs243865, MMP-2 rs2285053, MMP-9 rs3918242, or MMP-9 rs17576 with efficacy of ulinastatin in patients with SAP. Shesis software was adopted for analyzing single genotypes of MMP-2 and MMP-9 gene polymorphisms site A Generalized Multifactor Dimensionality Reduction (GMDR) model and a logistic regression analysis were used for analyzing effect of MMP-2 and MMP-9 gene polymorphisms on the efficacy of ulinastatin in treating patients with SAP. Results: CC genotype of MMP-2 gene rs243865 C>T was observed to have a better positive effect in promoting the efficacy of ulinastatin in comparison with CT and TT genotypes. Haplotype CCTG, CCTA, CTTG, and CTTA were combined by MMP-2 and MMP-9 gene polymorphisms which have the ability to increase the efficacy of ulinastatin in treating patients with SAP. MMP-2 gene rs243865 C>T site polymorphism was served as a favorable factor while the MMP-9 gene rs3918242 C>T site polymorphism was noticed as an unfavorable factor for the efficacy of ulinastatin in treating patients with SAP. Conclusion: The key findings clearly demonstrated that both the MMP-2 rs243865 and MMP-9 rs3918242 gene polymorphisms served as biological indicators for the efficacy of ulinastatin in treating patients with SAP.