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

• Published in: Journal of applied oral science Vol. 24; no. 4; pp. 366 - 375
• Main Authors: Trombone, Ana Paula Favaro, Cavalla, Franco, Silveira, Elcia Maria Varize, Andreo, Camile Bermejo, Francisconi, Carolina Favaro, Fonseca, Angélica Cristina, Letra, Ariadne, Silva, Renato Menezes, Garlet, Gustavo Pompermaier
• Format: Journal Article
• Language: English
• Published: Brazil Faculdade De Odontologia De Bauru - USP 01.07.2016; University of São Paulo
• Subjects: Adolescent; Adult; Case-Control Studies; Cytokines; Cytokines - analysis; Cytokines - genetics; Dentistry; DENTISTRY, ORAL SURGERY & MEDICINE; Female; Genetic; Genetic Association Studies; Genetic Markers; Genotype; Humans; Inflammation; Male; Matrix Metalloproteinase 1 - analysis; Matrix Metalloproteinase 1 - genetics; Matrix metalloproteinases; Middle Aged; Original; Periapical diseases; Periapical Diseases - genetics; Periapical granuloma; Periapical Granuloma - genetics; Polymorphism; Polymorphism, Genetic; Real-Time Polymerase Chain Reaction; Reference Values; Regression Analysis; Risk Factors; Statistics, Nonparametric; Up-Regulation; Young Adult; Matrix metalloproteinases; Cytokines; Periapical granuloma; Periapical diseases; Genetic; Inflammation; Polymorphism
• ISSN: 1678-7757; 1678-7765; 1678-7765; 1678-7757
• DOI: 10.1590/1678-775720160112

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. MMP1-1607 SNP and the mRNA levels of MMP-1, TNF-a, IFN-g, 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). 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-g, TNF-a, IL-21, IL-10, IL-9, and IL-4 were significant as complementary explanatory variables of MMP-1 expression. 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-a, 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.