MMP1-1607 polymorphism increases the risk for periapical lesion development through the upregulation MMP-1 expression in association with pro-inflammatory milieu elements

Increased matrix metalloproteinases (mmps) activity is a hallmark of periapical granulomas. however,the factors underlying the mmps expression modulation in healthy and diseased periapical tissues remains to be determined. objective: in this study,we evaluated the association between the mmp1-1607 polymorphism (rs1799750) and pro-inflammatory milieu elements with mmp-1 mrna levels in vivo. material and methods: mmp1-1607 snp and the mrna levels of mmp-1,tnf-α,ifn-γ,il-17a,il-21,il-10,il-4,il-9,and foxp3 were determined via realtimepcr in dna/rna samples from patients presenting periapical granulomas (n=111,for both genotyping and expression analysis) and control subjects (n=214 for genotyping and n=26 for expression analysis). the shapiro-wilk,fisher,pearson,chi-square ordinal least squares regression tests were used for data analysis (p<0.05 was considered statistically significant). results: the mmp1-1607 1g/2g and 1g/2g+2g/2g genotypes were significantly more prevalent in the patients than in controls,comprising a risk factor for periapical lesions development. mmp-1 mrna levels were higher in periapical lesions than in healthy periodontal ligament samples,as well as higher in active than in inactive lesions. the polymorphic allele 2g carriers presented a significantly higher mmp-1 mrna expression when compared with the 1g/1g genotype group. the ordered logistic regression demonstrated a significant correlation between the genetic polymorphism and the expression levels of mmp-1. additionally,the pro-and anti-inflammatory cytokines il-17a,ifn-γ,tnf-α,il-21,il-10,il-9,and il-4 were significant as complementary explanatory variables of mmp-1 expression. conclusion: the mmp1-1607 snp was identified as a risk factor for periapical lesions development,possibly due to its association with increased mmp-1 mrna levels in periapical lesions. the mmp-1 expression is also under the control of the inflammatory milieu elements,being the cytokines tnf-α,il-21,il-17a,and ifn-g associated with increased mmp-1 levels in periapical lesions,while il-10,il-9,or il-4 presented an inverse association. © 2016,faculdade de odontologia de bauru. all rights reserved.