Musculoskeletal Heritable Influences on Malocclusion

描述（由申请人提供）：本提案将证明影响颌骨长度以及颌骨肌肉大小和强度的遗传因素如何相互作用，以确定接受手术矫正颌面畸形的大量受试者中的错牙合表型。完成本提案的工作将使用主要研究者已经可用的实验室设施、设备和已建立的临床和分析合作。这一建议是第一个考虑遗传的影响，肌肉和骨骼是互动的，在生产变化颅面生长。翻译的结果，从这一建议将提供一个新的范例，包括考虑遗传到临床诊断和治疗计划的患者复杂的牙颌面畸形。我们发现，在咬肌中，纤维类型的大小和数量与垂直面维度的开和深咬错牙合的发展存在差异。 此外，左咬肌和右咬肌之间的纤维类型不同， 面部不对称的受试者，这可能会影响颞下颌关节功能障碍的发生，颞下颌关节功能障碍是面部疼痛的重要来源。这两项研究结果表明，面部肌肉和骨骼成分的生长和功能之间存在复杂的关系。最近的研究发现骨长度和肌肉力量表型的遗传影响。GIANT联盟（ANThropometric Traits的遗传调查）已经确定了180种影响人类身高的变异，人类表现和健康相关表型基因图谱（PHRP）总结了影响青春期和成年早期纤维类型和肌肉力量的基因或位点。组织假设是，在GIANT和PHRP财团中确定的骨长度和肌肉性能的基因变异影响咀嚼肌纤维组成和牙面变形的发展。我们的目标是确定特定的遗传变异和生长因子表达的差异与矢状和垂直牙面变形的发展之间的关联。这项建议将确定基因与咬肌纤维型组成的主题与牙面畸形（目标1）。这是第一个这样的研究，阐述哪些因素伴随引起咀嚼肌纤维型特性的变化，并与垂直颌骨的发展。目标1中确定的因素之间的变异性，沿着已知与颌骨长度差异相关的基因，将在目标2中用于测试候选基因中的多态性是否有助于牙面畸形和面部不对称的表型变异性。 公共卫生相关性：大约有一半的150万美国人与牙面畸形有颞下颌关节紊乱病作为一个相关的条件，但这些关节并发症的病因还没有得到很好的理解。正畸治疗占所有牙科治疗的8%，由于缺乏临床和基础科学信息，无法提供基于证据的治疗决策指导。新的研究，如这一个需要调查的基因和环境的相互作用的肌肉骨骼组织，以确定发展的错牙合畸形和牙面畸形的根本基础。

DESCRIPTION (provided by applicant): This proposal will demonstrate how heritable factors that influence jaw bone length and both the size and strength of jaw muscle interact to determine malocclusion phenotypes in a large population of subjects undergoing surgery to correct dentofacial deformities. Work toward completion of this proposal will be done with laboratory facilities, equipment and established clinical and analytical collaborations already available to the principle investigator. This proposal is the first to consider heritable influence of both muscle and bone to be interactive in producing variations in craniofacial growth. Translation of results from this proposal will provide a new paradigm to include the consideration of heritability into clinical diagnosis and treatment planning for patients with complex dentofacial deformities. We find that in masseter muscle, size and number of fiber types are differentially associated with the development of open and deep bite malocclusion of the vertical facial dimension. Also, fiber types differ between left and right masseter muscles in subjects with facial asymmetry, which may affect occurrence of temporomandibular joint dysfunction that is a significant source of facial pain. Both findings indicate complex relationships between growth and function of muscular and skeletal components of the face. There are recent findings for heritable influences on bone length and muscle strength phenotypes. The GIANT consortium (Genetic Investigation of ANThropometric Traits) has identified 180 variants which affect human height, and the Human Gene Map for Performance and Health-Related Phenotypes (PHRP) has summarized genes or loci which affect fiber types and muscle strength during adolescence and young adulthood. The organizing hypothesis is that gene variants for bone length and muscular performance identified in the GIANT and PHRP consortiums influence the development of masticatory muscle fiber composition and dentofacial deformations. Our goal is to identify associations between specific genetic variations and differences in growth factor expression with the development of sagittal and vertical dentofacial deformations. This proposal will identify genes associated with masseter muscle fiber-type composition in subjects with dentofacial deformities (Aim 1). This is the first such study to elaborate which factors concomitantly elicit changes in masticatory muscle fiber-type properties and associate with vertical jaw development. Variability among factors identified in Aim 1, along with genes known to associate with differences in jaw length, will be used in Aim 2 to test if polymorphisms in candidate genes contribute to phenotypic variability in dentofacial deformities and facial asymmetry. PUBLIC HEALTH RELEVANCE: About half the 1.5 million Americans with dentofacial deformities have TMD as an associated condition, but the etiology of these joint complications is not well understood. For orthodontic treatment, which comprises 8% of all dental treatments, it is not possible to provide evidence-based guidance of treatment decisions due to the lack of clinical and basic science information. New studies such as this one are needed to investigate gene and environmental interactions of musculoskeletal tissues to determine the fundamental basis for development of malocclusion and dentofacial deformities.