ObjectivesRecurrent 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 methodsNinety‐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.ResultsMMP‐9 rs11697325 was significantly associated with RAS, with an increase in the AA genotype in patients, determined using χ2 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.ConclusionsThis 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.