title: ACTN3 R577X genotypes associate with Class II and deepbite malocclusions.
abstract: BACKGROUND
  α-Actinins are myofibril anchor proteins that influence the contractile properties of skeletal muscles. 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 (ie, changing 577RR to 577XX, the R577X polymorphism) results in the absence of α-actinin-3 in about 18% of Europeans, diminishes fast contractile ability, enhances endurance performance, and reduces bone mass or bone mineral density. We have examined ACTN3 expression and genetic variation in the masseter muscle of orthognathic surgery patients to determine the genotype associations with malocclusion.
  
  
  METHODS
  Clinical information, masseter muscle biopsies, and saliva samples were obtained from 60 subjects. Genotyping for ACTN3 single nucleotide polymorphisms, real-time polymerase chain reaction quantitation of muscle gene message, and muscle morphometric fiber type properties were compared to determine statistical differences between genotype and phenotype.
  
  
  RESULTS
  Muscle mRNA expression level was significantly different for ACTN3 single nucleotide polymorphism genotypes (P <0.01). The frequency of ACTN3 genotypes was significantly different for the 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 diameters of fast type II fibers in masseter muscles (P = 0.002).
  
  
  CONCLUSIONS
  ACTN3 577XX is overrepresented in subjects with skeletal Class II malocclusion, suggesting a biologic influence during bone growth. ACTN3 577XX is underrepresented in subjects with deepbite malocclusion, suggesting that muscle differences contribute to variations in vertical facial dimensions.
authors.affiliation: Resident, Department of Orthodontics, Temple University, Philadelphia, Pa.
authors.forename: Brian
authors.initials: B
authors.lastname: Zebrick
authors.affiliation: Fellow, Department of Orthodontics, Temple University, Philadelphia, Pa.
authors.forename: Teesit
authors.initials: T
authors.lastname: Teeramongkolgul
authors.affiliation: Resident, Oral and Maxillofacial Department, Université Lille Nord de France, Lille, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Nicot
authors.affiliation: Research assistant professor, Department of Orthodontics, Temple University, Philadelphia, Pa.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Horton
authors.affiliation: Professor, Department of Oral and Maxillofacial, Université Lille Nord de France, Lille, France; UDSL, Roger Salengro Hospital, CHU; and INSERM U 1008, Controlled Drug Delivery Systems and Biomaterials, Lille, France.
authors.forename: Gwenael
authors.initials: G
authors.lastname: Raoul
authors.affiliation: Professor and head, Department of Oral and Maxillofacial Surgery, Université Lille Nord de France, Lille, France; UDSL, Roger Salengro Hospital, CHU; and INSERM U 1008, Controlled Drug Delivery Systems and Biomaterials, Lille, France.
authors.forename: Joel
authors.initials: J
authors.lastname: Ferri
authors.affiliation: Associate professor, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pa.
authors.forename: Alexandre R
authors.initials: AR
authors.lastname: Vieira
authors.affiliation: Professor, Department of Orthodontics, Temple University, Philadelphia, Pa. Electronic address: jjs6@dental.temple.edu.
authors.forename: James J
authors.initials: JJ
authors.lastname: Sciote
mesh_terms: D000185:Actinin / Q000235:genetics*; D001120:Arginine / Q000235:genetics*; D001706:Biopsy; D018388:Codon, Terminator / Q000235:genetics; D003596:Cytosine; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008312:Malocclusion, Angle Class II / Q000235:genetics*; D008406:Masseter Muscle / Q000378:metabolism / Q000473:pathology; D018656:Muscle Fibers, Fast-Twitch / Q000648:ultrastructure; D018485:Muscle Fibers, Skeletal / Q000145:classification / Q000473:pathology; D057887:Overbite / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012463:Saliva / Q000737:chemistry; D013941:Thymine; D055815:Young Adult
chemical_list: C118456:ACTN3 protein, human; D018388:Codon, Terminator; D000185:Actinin; D003596:Cytosine; D001120:Arginine; D013941:Thymine