Musculoskeletal Heritable Influences on Malocclusion

描述(由申请人提供)：这项提案将展示影响颌骨长度和颌肌大小和力量的遗传因素如何相互作用，以确定在接受手术矫正牙面畸形的大量受试者中的错牙合表型。完成这项建议的工作将利用实验室设施、设备以及已建立的临床和分析合作关系来完成，主要研究人员已经可以使用。这一建议首次考虑到肌肉和骨骼的可遗传影响在头面部生长的变化中是相互作用的。这项建议的结果翻译将提供一个新的范例，将遗传性纳入复杂牙面畸形患者的临床诊断和治疗计划中。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放和深咬合错合的发生有不同的关联。此外，左右咬肌之间的纤维类型也不同 面部不对称的受试者，这可能会影响颞颌关节功能障碍的发生，这是面部疼痛的一个重要来源。这两项发现都表明，面部肌肉和骨骼成分的生长和功能之间存在复杂的关系。最近有关于遗传影响骨骼长度和肌肉力量表型的发现。这个巨大的财团(人体测量特征的遗传调查)已经确定了180个影响身高的变异，而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青年时期纤维类型和肌肉力量的基因或基因座。组织假说是，在巨型和PHRP联合体中发现的骨骼长度和肌肉性能的基因变异影响咀嚼肌纤维组成和牙面部变形的发展。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面和垂直面畸形的发展之间的联系。这项建议将确定牙面部畸形受试者中与咬肌纤维类型组成相关的基因(目标1)。这是第一次详细阐述哪些因素同时引起咀嚼肌纤维类型属性的变化，并与垂直颌骨发育相关的研究。目标1中确定的因素之间的可变性，以及已知的与颌骨长度差异有关的基因，将在目标2中用于测试候选基因的多态是否有助于牙面部畸形和面部不对称的表型可变性。 公共卫生相关性：在150万患有牙面部畸形的美国人中，大约有一半的人患有TMD作为相关疾病，但这些关节并发症的病因尚不清楚。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，无法为治疗决定提供循证指导。需要像这样的新研究来研究肌肉骨骼组织的基因和环境的相互作用，以确定错(牙合)和牙面畸形发生的基本基础。

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.