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Influence of Matrix Metalloproteinase-1 Gene −1607 (1G/2G) (rs1799750) Promoter Polymorphism on Circulating Levels of MMP-1 in Chronic Pancreatitis

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Abstract

This study investigated the role of −1607 (1G/2G) (rs1799750) polymorphism of the MMP-1 gene in chronic pancreatitis. We genotyped 100 patients with chronic pancreatitis and 100 control subjects using tetra-primer ARMS-PCR followed by agarose gel electrophoresis. Serum levels of MMP-1 were determined by Elisa. Statistical analysis was applied to test the significance of the results. The genotypic and allelic distribution varied significantly between the disease group and the control subjects [OD = 1.981 (1.236–3.181), p = 0.004]. MMP-1 levels were higher in subjects homozygous for the 2G allele than in subjects with the 1G allele. The present study revealed a significant association of the MMP-1 −1607 1G/2G (rs1799750) gene promoter polymorphism with chronic pancreatitis, and it can be considered a biological marker in the etiology of chronic pancreatitis.

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References

  • Arakaki PA, Marques MR, Santos MC (2009) MMP-1 polymorphism and its relationship to pathological processes. J Biosci 34:313–320

    Article  PubMed  CAS  Google Scholar 

  • Astolfi CM, Shinohara AL, da Silva RA, Santos MC, Line SR, de Souza AP (2006) Genetic polymorphisms in the MMP-1 and MMP-3 gene may contribute to chronic periodontitis in a Brazilian population. J Clin Periodontol 33:699–703

    Article  PubMed  CAS  Google Scholar 

  • Benyon D, Arthur MJP (2001) Extracellular matrix degradation and the role of stellate cells. Semin Liver Dis 21:373–384

    Article  PubMed  CAS  Google Scholar 

  • Birkedal-Hansen H, Moore WG, Bodden MK, Windsor LJ, Birkedal-Hansen B, DeCarlo A, Engler JA (1993) Matrix metalloproteinases: a review. Crit Rev Oral Biol Med 4:197–250

    PubMed  CAS  Google Scholar 

  • Chen Y, Nixon NB, Dawes PT, Mattey DL (2012) Influence of variations across the MMP-1 and -3 genes on the serum levels of MMP-1 and -3 and disease activity in rheumatoid arthritis. Genes Immun 13:29–37

    Article  PubMed  CAS  Google Scholar 

  • Clemens DL, Mahan KJ (2010) Alcoholic pancreatitis: lessons from the liver. World J Gastroenterol 16:1314–1320

    Article  PubMed  CAS  Google Scholar 

  • Coon CI, Fiering S, Gaudet J, Wyatt CA, Brinckerhoff CE (2009) Site controlled transgenic mice validating increased expression from human matrix metalloproteinase (MMP-1) promoter due to a naturally occurring SNP. Matrix Biol 28:425–431

    Article  PubMed  CAS  Google Scholar 

  • Domínguez-Muñoz JE, Manes G, Pieramico O, Büchler M, Malfertheiner P (1995) Effect of pancreatic ductal and parenchymal changes on exocrine function in chronic pancreatitis. Pancreas 10:31–35

    Article  PubMed  Google Scholar 

  • Fiedorczyk M, Klimiuk PA, Sierakowski S, Gindzienska-Sieskiewicz E, Chwiecko J (2006) Serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in patients with early rheumatoid arthritis. J Rheumatol 33:1523–1529

    PubMed  CAS  Google Scholar 

  • Gearing AJH, Beckett P, Christodoulou M, Churchill M, Clements J, Davidson AH, Drummond AH, Galloway WA, Gilbert R, Gordon JL, Leber TM, Mangan M, Miller K, Nayee P, Owen K, Patel S, Thomas W, Wells G, Wood LM, Woolley K (1994) Processing of tumour necrosis factor-alpha precursor by metalloproteinases. Nature 370:555–557

    Article  PubMed  CAS  Google Scholar 

  • Ghilardi G, Biondi ML, DeMonti M, Turri O, Guagnellini E, Scorza R (2002) Matrix metalloproteinase-1 and matrix metalloproteinase-3 gene promoter polymorphisms are associated with carotid artery stenosis. Stroke 33:2408–2412

    Article  PubMed  CAS  Google Scholar 

  • Green MJ, Gough AK, Devlin J, Smith J, Astin P, Taylor D, Emery P (2003) Serum MMP-3 and MMP-1 and progression of joint damage in early rheumatoid arthritis. Rheumatology 42:83–88

    Article  PubMed  CAS  Google Scholar 

  • Hinoda Y, Okayama N, Takano N, Fujimura K, Suehiro Y, Hamanaka Y, Hazama S, Kitamura Y, Kamatani N, Oka M (2002) Association of functional polymorphisms of matrix metalloproteinase (MMP)-1 and MMP-3 genes with colorectal cancer. Int J Cancer 102:526–529

    Article  PubMed  CAS  Google Scholar 

  • Hirata H, Okayama N, Naito K, Inoue R, Yoshihiro S, Matsuyama H, Suehiro Y, Hamanaka Y, Hinoda Y (2004) Association of a haplotype of matrix metalloproteinase (MMP)-1 and MMP-3 polymorphisms with renal cell carcinoma. Carcinogenesis 25:2379–2384

    Article  PubMed  CAS  Google Scholar 

  • Itagaki M, Kubota T, Tai H, Shimada Y, Morozumi T, Yamazaki K (2004) Matrix metalloproteinase-1 and -3 gene promoter polymorphisms in Japanese patients with periodontitis. J Clin Periodontol 31:764–769

    Article  PubMed  CAS  Google Scholar 

  • Kihara Y, Tashiro M, Nakamura H, Yamaguchi T, Yoshikawa H, Otsuki M (2001) Role of TGF-β1, extracellular matrix, and matrix metalloproteinase in the healing process of the pancreas after induction of acute necrotizing pancreatitis using arginine in rats. Pancreas 23:288–295

    Article  PubMed  CAS  Google Scholar 

  • Lahiri DK, Nurnberger JI Jr (1991) A rapid non-enzymatic method for the preparation of HMW DNA from blood. Nucleic Acids Res 19:5444

    Article  PubMed  CAS  Google Scholar 

  • Li L, Bachem MG, Zhou S, Sun Z, Chen J, Siech M, Bimmler D, Graf R (2009) Pancreatitis-associated protein inhibits human pancreatic stellate cell MMP-1 and -2, TIMP-1 and -2 secretion and RECK expression. Pancreatology 9:99–110

    Article  PubMed  CAS  Google Scholar 

  • Mews P, Phillips P, Fahmy R, Korsten M, Pirola R, Wilson J, Apte M (2002) Pancreatic stellate cells respond to inflammatory cytokines: potential role in chronic pancreatitis. Gut 50:535–541

    Article  PubMed  CAS  Google Scholar 

  • Midha S, Khajuria R, Shastri S, Kabra M, Garg PK (2010) Idiopathic chronic pancreatitis in India: phenotypic characterisation and strong genetic susceptibility due to SPINK1 and CFTR gene mutations. Gut 59:800–807

    Article  PubMed  CAS  Google Scholar 

  • Müller-Pillasch F, Gress TM, Yamaguchi H, Geng M, Adler G, Menke A (1997) The influence of transforming growth factor 1 on the expression of genes coding for matrix metalloproteinases and tissue inhibitors of metalloproteinases during regeneration from cerulein-induced pancreatitis. Pancreas 15:168–175

    Article  PubMed  Google Scholar 

  • Nagase H, Woessner JF Jr (1999) Matrix metalloproteinases. J Biol Chem 274:21491–21494

    Article  PubMed  CAS  Google Scholar 

  • Planello AC, Campos MIG, Meloto CB, Secolin R, Rizatti-Barbosa CM, Line SRP, de Souza AP (2011) Association of matrix metalloproteinase gene polymorphism with temporomandibular joint degeneration. Eur J Oral Sci 119:1–6

    Article  PubMed  CAS  Google Scholar 

  • Ravanti L, Kähäri VM (2000) Matrix metalloproteinases in wound repair (review). Int J Mol Med 6:391–407

    PubMed  CAS  Google Scholar 

  • Rutter JL, Mitchell TI, Butticè G, Meyers J, Gusella JF, Ozelius LJ, Brinckerhoff CE (1998) A single nucleotide polymorphism in the matrix metalloproteinase-1 promoter creates an Ets binding site and augments transcription. Cancer Res 58:5321–5325

    PubMed  CAS  Google Scholar 

  • Segura-Valdez L, Pardo A, Gaxiola M, Uhal BD, Becerril C, Selman M (2000) Upregulation of gelatinases A and B, collagenases 1 and 2, and increased parenchymal cell death in COPD. Chest 117:684–694

    Article  PubMed  CAS  Google Scholar 

  • Tang LJ, Chen XF, Zhu M, Jiang JJ, Lu XB, Du YX, Wang B, Fang CF, Xue YS, Shen WF (2007) Matrix metalloproteinase-1, -3, and -9 gene polymorphisms and the risk of idiopathic dilated cardiomyopathy in a Chinese Han population. Clin Biochem 40:1427–1430

    Article  PubMed  CAS  Google Scholar 

  • Tasaki K, Shintani Y, Saotome T, Andoh A, Fujiyama Y, Hozawa S, Bamba T (2003) Pro-inflammatory cytokine-induced matrix metalloproteinase-1 (MMP-1) secretion in human pancreatic periacinar myofibroblasts. Pancreatology 3:414–421

    Article  PubMed  CAS  Google Scholar 

  • Terashima M, Akita H, Kanazawa K, Inoue N, Yamada S, Ito K, Matsuda Y, Takai E, Iwai C, Kurogane H, Yoshida Y, Yokoyama M (1999) Stromelysin promoter 5A/6A polymorphism is associated with acute myocardial infarction. Circulation 99:2717–2719

    Article  PubMed  CAS  Google Scholar 

  • Vincenti MP, Brinckerhoff CE (2002) Transcriptional regulation of collagenase (MMP-1, MMP-13) genes in arthritis: integration of complex signaling pathways for the recruitment of gene-specific transcription factors. Arthritis Res 4:157–164

    Article  PubMed  CAS  Google Scholar 

  • Ye S (2000) Polymorphism in matrix metalloproteinase gene promoters: implication in regulation of gene expression and susceptibility of various diseases. Matrix Biol 19:623–629

    Article  PubMed  CAS  Google Scholar 

  • Yokota T, Denham W, Murayama K, Pelham C, Joehl R, Bell RH Jr (2002) Pancreatic stellate cell activation and MMP production in experimental pancreatic fibrosis. J Surg Res 104:106–111

    Article  PubMed  CAS  Google Scholar 

  • Zhang BB, Cai WM, Weng HL, Hu ZR, Lu J, Zheng M, Liu RH (2003) Diagnostic value of platelet derived growth factor-BB, transforming growth factor-b1, matrix metalloproteinase-1, and tissue inhibitor of matrix metalloproteinase-1 in serum and peripheral blood mononuclear cells for hepatic fibrosis. World J Gastroenterol 9:2490–2496

    PubMed  CAS  Google Scholar 

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Acknowledgments

The authors acknowledge financial support from the University Grants Commission (UGC), New Delhi. The authors are also thankful to the Department of Biotechnology, New Delhi, for providing laboratory facilities.

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Correspondence to A. Venkateshwari.

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Sri Manjari, K., Nallari, P., Balakrishna, N. et al. Influence of Matrix Metalloproteinase-1 Gene −1607 (1G/2G) (rs1799750) Promoter Polymorphism on Circulating Levels of MMP-1 in Chronic Pancreatitis. Biochem Genet 51, 644–654 (2013). https://doi.org/10.1007/s10528-013-9594-9

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  • DOI: https://doi.org/10.1007/s10528-013-9594-9

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