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Mandibular retrognathism is a type of malocclusion that refers to an abnormal posterior position of the mandible as a result of a developmental abnormality. From the literature, it is evident that the mandibular growth pattern is determined by the intramembranous ossification of the mandibular body and endochondral ossification of the condyle. Matrilin-1 is a cartilage extracellular matrix protein, and matrilin-1 gene (MATN1) polymorphisms have been found to be involved in dental malocclusions of humans. In this study, we aimed to examine the association between MATN1 polymorphisms and the risk of mandibular retrognathism, in a case-control study with a South Indian population.Eighty-one patients with mandibular retrognathism (SNB, <78°) and 71 controls having an orthognathic mandible (SNB, 80° ± 2°) were recruited. In both the patient and control groups, subjects with an orthognathic maxilla (SNA, 82° ± 2°) were included. Three single nucleotide polymorphisms of the MATN1 gene (rs1149048, rs1149042, and rs1065755) were genotyped using polymerase chain reaction-restriction fragment length polymorphism. The statistical association analysis was performed using the chi-square test. Pair-wise linkage disequilibrium was computed, and haplotypes were compared between subjects and controls. Nonparametric tests were used to compare cephalometric measurements between groups.No polymorphic site deviated from Hardy-Weinberg equilibrium in the controls. The rs1149042 genotypes and alleles were found to be associated with reduced risk of mandibular retrognathism. Furthermore, rs1149042 genotypes were associated with mandibular measurements (SNB and ANB). There was no strong and consistent linkage disequilibrium linkage disequilibrium across two different single nucleotide polymorphisms and haplotypes were not associated with mandibular retrognathism.The results of our study suggest an association between the MATN1 gene polymorphisms and mandibular retrognathism.The matrilins are a family of noncollagenous extracellular matrix proteins.We aimed to evaluate MATN1 gene polymorphisms as a risk factor for mandibular retrognathism.Polymorphisms of MATN1 gene (rs1149048, rs114904, and rs1065755) were analyzed for 81 subjects and 71 controls.The rs1149042 genotypes and alleles were associated with reduced risk of mandibular retrognathism.The rs1149048 genotypes showed significant differences in mandibular corpus length.