ACTN3 R577X GENOTYPES ASSOCIATE WITH CLASS II AND DEEP BITE MALOCCLUSIONS

Abstract

Alpha-actinins are myofibril anchor proteins, which influence contractile properties of skeletal muscle. ACTN2 is expressed in slow type I and fast type II fibers whereas ACTN3 is expressed only in fast fibers. ACTN3 homozygosity for the 577X stop codon (i.e. changing 577RR to 577XX - the R577X polymorphism) results in the absence of alpha-actinin-3 in about 18% of Europeans, diminished fast contractile ability, enhanced endurance performance, and reduced bone mass or bone mineral density. We have examined ACTN3 expression and genetic variation in masseter muscle of orthognathic surgery patients to determine genotype associations with malocclusion. To determine the associations between genotypes and malocclusions, clinical information, masseter muscle biopsies, and saliva samples were obtained from 60 subjects. Genotyping for ACTN3 SNPs, RT-PCR quantitation of muscle gene message, and muscle morphometric fiber type properties were compared to determine statistical differences between genotype and phenotype. We found muscle mRNA expression level was significantly different for ACTN3 SNP genotypes (p<0.01). The frequency of ACTN3 genotypes was significantly different for sagittal and vertical classifications of malocclusion with the clearest association being elevated 577XX genotype in skeletal Class II malocclusion (p = 0.003). This genotype also resulted in significantly smaller diameter of fast type II fibers in masseter muscle (p=0.002). In conclusion, ACTN3 577XX is overrepresented in skeletal Class II malocclusion, suggesting a biologic influence during bone growth. ACTN3 577XX is underrepresented in deep bite malocclusion, suggesting muscle differences contribute to variations in vertical facial dimensions.