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MMP-2 and MMP-9 gene polymorphisms act as biological indicators for ulinastatin efficacy in patients with severe acute pancreatitis.

ABSTRACT: 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.

SUBMITTER: Ling L

PROVIDER: S-EPMC6587626 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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MMP-2 and MMP-9 gene polymorphisms act as biological indicators for ulinastatin efficacy in patients with severe acute pancreatitis.

Ling Lan L Li Yan Y Li Hong H Li Wen W Zhang Hong-Bo HB

Medicine 20190601 24

<h4>Background</h4>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.<h4>Methods</h4>A total of 235 patients with SAP were treated by intravenous drip of ...[more]

PMID: 31192912

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Project description:ObjectivesThe prognosis of severe acute pancreatitis (SAP) patients is closely related to early nutritional support. It is well-established that changes in glutamine (Gln), an important amino acid and nutritional supplement, can reflect disease severity. However, no consensus has been reached on the role of Gln nutrition therapy for SAP patients. We conducted this systematic review and meta-analysis to summarize and evaluate the advantages of Gln supplementation in SAP.MethodsPubMed, Web of Science, the Embase, Cochrane Library, and Chinese databases (CNKI, SinoMed, Wanfang, and VIP) were systematically searched for eligible studies that included glutamine supplementation in SAP patients from inception to October 31 2021, excluding non-SAP studies. Primary outcome measures included mortality, APACHE II score, complications, and length of hospital stay. The meta-analysis was registered with PROSPERO (CRD42021288371) and was conducted using Review Manager and Stata softwares.ResultsThis meta-analysis included 30 randomized controlled trials (RCTs) with a total of 1,201 patients. Six primary outcomes and six secondary outcomes were analyzed. For the primary outcomes, Gln supplementation was associated with lower mortality (OR = 0.38, 95% CI: 0.21-0.69, P = 0.001), total hospital stay (MD = -3.41, 95% CI: -4.93 to -1.88, P < 0.0001) and complications (OR = 0.45, 95% CI: 0.31-0.66, P < 0.0001) compared with conventional nutrition. Further subgroup analysis found that parenteral glutamine was more effective in reducing mortality. In terms of secondary outcomes, Gln supplementation helped restore liver, kidney and immune function, with significantly increased serum albumin (SMD = 1.02, 95% CI: 0.74-1.31, P < 0.00001) and IgG levels (MD = 1.24, 95% CI: 0.82-1.67, P < 0.00001), and decreased serum creatinine (Scr) (MD = -12.60, 95% CI: -21.97 to -3.24, P = 0.008), and inflammatory indicators such as C-reaction protein (CRP) (SMD = -1.67, 95% CI: -2.43 to -0.90, P < 0.0001).ConclusionAlthough Gln supplementation is not routinely recommended, it is beneficial for SAP patients. Indeed, glutamine nutrition has little effect on some indicator outcomes but contributes to improving the prognosis of this patient population.Systematic Review Registration: PROSPERO (york.ac.uk). Unique Identifier: CRD42021288371.

Project description:IntroductionSevere acute pancreatitis (AP) is associated with high morbidity and mortality. Early prediction of severe AP is needed to improve patient outcomes. The aim of the present study was to find novel cytokines or combinations of cytokines that can be used for the early identification of patients with AP at risk for severe disease.MethodsWe performed a prospective study of 163 nonconsecutive patients with AP, of whom 25 had severe AP according to the revised Atlanta criteria. Admission serum levels of 48 cytokines and growth factors were determined using Bio-Plex Pro Human Cytokine Assay 21-plex and 27-plex magnetic bead suspension panels. Admission plasma levels of C-reactive protein (CRP), creatinine and calcium were measured for comparison. In subgroup analyses, we assessed the cytokine profiles of patients with severe AP (n = 14) who did not have organ dysfunction (OD) upon admission (modified Marshall score <2).ResultsOf 14 cytokines elevated in the severe AP group, interleukin 6 (IL-6) and hepatocyte growth factor (HGF) levels were independent prognostic markers of severe AP. IL-6, HGF and a combination of them predicted severe AP with sensitivities of 56.0%, 60.0% and 72.0%, respectively, and specificities of 90.6%, 92.8% and 89.9%, respectively. The corresponding positive likelihood ratio (LR+) values were 5.9, 8.3 and 7.1, respectively. The predictive values of CRP, creatinine and calcium were comparable to those of the cytokines. In subgroup analyses of patients with severe AP and without OD upon admission, we found that IL-8, HGF and granulocyte colony-stimulating factor (G-CSF) levels predicted the development of severe AP, with G-CSF being the most accurate cytokine at a sensitivity of 35.7%, a specificity of 96.1% and a LR+ of 9.1.ConclusionsIL-6 and HGF levels upon admission have prognostic value for severe AP which is similar to levels of CRP, creatinine and calcium. Although IL-6 and HGF, as either single or combined markers, were not perfect in identifying patients at risk for severe AP, the possibility that combining them with novel prognostic markers other than cytokines might improve prognostic accuracy needs to be studied. The accuracy of IL-8, HGF and G-CSF levels in predicting severe AP in patients without clinical signs of OD upon admission warrants larger studies.

Dataset Information

MMP-2 and MMP-9 gene polymorphisms act as biological indicators for ulinastatin efficacy in patients with severe acute pancreatitis.

Publications

MMP-2 and MMP-9 gene polymorphisms act as biological indicators for ulinastatin efficacy in patients with severe acute pancreatitis.

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