Synergistic effect of stromelysin-1 (matrix metalloproteinase-3) promoter (-1171 5A->6A) polymorphism in oral submucous fibrosis and head and neck lesions

Abstract

BackgroundMatrix metalloproteinases (MMPs) are enzymes that degrade all the components of extra cellular matrix and collagen. Various types of MMPs are known to be expressed and activated in patients with oral submucous fibrosis (OSMF) as well as head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to asses the association of the single nucleotide polymorphism (SNP) adenosine insertion/deletion polymorphism (-1171 5A->6A) in the MMP-3 promoter region in these lesions.MethodsMMP-3 SNP was genotyped by polymerase chain reaction-restriction fragment polymorphism (PCR-RFLP) analysis in a case control study consisting of 362 participants; 101 cases of OSMF, 135 of HNSCC and 126 controls, compared for age, sex and habits. ROC distribution was plotted to assess the contributions of genetic variation in MMP-3 genotypes with relation to age.ResultsAnalysis of MMP 3 (-1171 5A->6A) polymorphism revealed the frequency of 5A allele in OSMF, HNSCC and controls to be 0.15, 0.13 and 0.07, respectively. A significant difference was found in 5A genotype frequency between OSMF (5A genotype frequency = 0.15, p = 0.01, OR = 2.26, 95% CI = 1.22-4.20) and in controls (5A genotype frequency 0.07) as well as HNSCC (5A genotype frequency 0.13, p = 0.03,95%CI = 1.06-3.51) and controls (5A genotype frequency = 0.07) In this study, 5A genotype had greater than two fold risk for developing OSMF (OR = 2.26) and nearly the same in case of HNSCC (OR = 1.94) as compared to controls. In patients with OSMF as well as HNSCC, the ROC analysis between the MMP-3 genotype and age, 6A/6A allele was found to be significant in patients both over and under 45 years of age; while the 5A/5A carrier alleles showed an association only in patients less than 45 years of age.ConclusionsThis study concluded that the expression of MMP-3 genotype associated with the 5A alleles, it may have an important role in the susceptibility of the patients to develop OSMF and HNSCC.

Matrix metalloproteinase gene polymorphisms and susceptibility to systemic sclerosis

“…They may include damage to the ECM proteins, alterations in the mechanisms responsible for inhibition of the calcification process, and abnormalities in the mitochondrial calcium and phosphate levels (Gutierrez and Wetter, 2012). It has been previously reported that the 6A allele has two-folds lower promoter activity than the 5A allele (Chaudhary et al, 2010). This lower transcriptional activity may be responsible for protecting against calcinosis development in SSc patients with the 6A/6A genotype.…”

“…Moreover, in the -1171 position of the MMP3 promoter region, an insertion of one adenosine gives rise to alleles having either six (6A) or five adenosines (5A); it has been previously reported that individuals with the 6A/6A genotype may have decreased MMP-3 expression (Chaudhary et al, 2010). Finally, MMP9 harbors a C-to-T transition at the -1562 position; the T allele has been associated with higher transcriptional activity compared to the C allele (Skarmoutsou et al, 2011).…”

A study on genetic polymorphism in Matrix Metalloproteinases-3 in oral submucous fibrosis patients and in healthy individuals

“…This result is similar to the study conducted by Choudhary et.al, which showed a significant difference in 5A allele frequency between OSF and HNSCC as compared with controls. The study concluded that the 5A genotype had a more than two fold risk for OSF (OR = 2.26) and little less in HNSCC (OR = 1.94) in relation to the control group [28]. Association of Duration of the habit with stages of OSF were statistically significant p = 0.01 and p = 0.04 with 5A/5A, 5A/6A,6A/6A genotypes Thus the association of duration of the habit and stage of OSF was significant with the genotypes Fig.…”

“…In a previously conducted study by Choudhary et.al with the MMP-3 gene polymorphism in OSF and HNSCC there was a significant difference in the MMP-3 genotype distribution between the areca nut with tobacco chewers and the non -chewers both in OSMF and HNSCC [28].…”

“…This is also important in the view that the individual mechanisms operating at various stages of the disease initial, intermediate and advanced need further study in order to establish an association with polymorphisms and to propose appropriate therapeutic interventions [29]. Chaudhary and colleagues in their study found that the 5A allele might play an important role in the susceptibility to HNC, as individuals with 5A/5A genotype had nearly two fold risk of HNSCC (OR = 1.94) when compared to controls [28]. However, Tu and colleagues found that the 5A/5A genotype was associated with the risk of oral submucous fibrosis but not OSCC [9].…”