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  • Title: MMP gene polymorphisms as contributors for cleft lip/palate: association with MMP3 but not MMP1.
    Author: Letra A, Silva RA, Menezes R, Astolfi CM, Shinohara A, de Souza AP, Granjeiro JM.
    Journal: Arch Oral Biol; 2007 Oct; 52(10):954-60. PubMed ID: 17537400.
    Abstract:
    OBJECTIVE: Orofacial clefts result from failures of developing embryonic facial and palatal processes to either completely merge or fuse. Normal development of the facial primordia requires remodelling of the extracellular matrix, which is mediated in part by the matrix metalloproteinases (MMPs). MMPs can be considered a group of candidate proteins for the etiology of cleft lip with or without cleft palate (CL/P) due to their role in craniofacial modelling. The purpose of this study was to determine if polymorphisms in MMP1 and MMP3 gene promoters were associated with CL/P. DESIGN: DNA was extracted from buccal epithelial cells and genotypes were obtained from CL/P cases and controls through PCR with allele-specific primers (MMP3, n=333) and restriction-fragment length polymorphism techniques (MMP1, n=395). RESULTS: Significant differences between cases and controls were observed for MMP3 [5A/6A allele frequencies (p=0.00001) and genotype frequencies (p=0.00001)]; and between cleft types and controls (p=0.00001 for CL/P; p=0.04 for CP). No significant differences were found for MMP1 allele and genotype frequencies between cases and controls or between cleft types and controls. CONCLUSIONS: An association between a polymorphism in MMP3 gene and CL/P has been observed. Although the extent to which this polymorphism may actually contribute to the affected cleft status is yet to be clarified, polymorphisms of MMP genes may be good candidates as genetic factors for their role in active ECM remodelling.
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