Association of MMP but not TIMP-1 gene polymorphisms with recurrent aphthous stomatitis

Oral Dis. 2014 Oct;20(7):693-9. doi: 10.1111/odi.12190. Epub 2013 Nov 6.

Abstract

Objectives: Recurrent aphthous stomatitis (RAS) is a common oral inflammatory disease induced by genetic and environmental factors. Gelatinases (MMP-2 and MMP-9) and their natural inhibitor TIMP-1 are active players in the inflammatory process. We aimed to determine whether inheritance of specific MMP-2, MMP-9, or TIMP-1 gene polymorphisms is associated with RAS susceptibility.

Subjects and methods: Ninety-six RAS patients and 153 healthy controls were studied. Five polymorphisms were genotyped: rs17576, rs3918242, and rs11697325 in MMP-9, MMP-2 rs2285053, and TIMP-1 rs6609533. Association was assessed by logistic regression analysis after adjustment for confounding factors. Linkage disequilibrium (LD) was assessed using the Haploview program.

Results: MMP-9 rs11697325 was significantly associated with RAS, with an increase in the AA genotype in patients, determined using χ(2) analysis (OR = 2.3, P = 0.006) and adjusted regression analysis (OR = 3.1, P = 0.009). MMP-9 rs11697325 and rs17576 showed strong LD (D' = 0.95), with an increase in the AA haplotype (P = 0.023) and a decrease in the GA haplotype (P = 0.015) in patients.

Conclusions: This is the first study to investigate the association of MMPs or TIMP-1 with RAS. We found a significant association between MMP-9 rs11697325 polymorphisms and RAS. Confirmatory studies in other populations and functional investigations are needed to determine the role of these genes in RAS.

Keywords: matrix metalloproteinase; polymorphism; recurrent aphthous stomatitis; tissue inhibitors of metalloproteinases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Female
  • Haplotypes
  • Humans
  • Linkage Disequilibrium
  • Male
  • Matrix Metalloproteinase 2 / genetics*
  • Matrix Metalloproteinase 9 / genetics*
  • Polymorphism, Single Nucleotide*
  • Stomatitis, Aphthous / enzymology*
  • Stomatitis, Aphthous / genetics*
  • Tissue Inhibitor of Metalloproteinase-1 / genetics*

Substances

  • TIMP1 protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9

Supplementary concepts

  • Sutton disease 2