George Ashwin Mathew, Priyadharsini Jayaseelan Vijayashree, Felicita Sumathi, Sundari Shantha, Subramanian Aravind Kumar
Department of Orthodontics and Dentofacial Orthopaedics, Saveetha Institute of Medical and Technical Sciences, Saveetha Dental College and Hospitals, SIMATS University, Chennai, India.
Clinical Genetics Lab, Saveetha Institute of Medical and Technical Sciences, Saveetha Dental College and Hospitals, SIMATS University, Chennai, India.
Orthod Craniofac Res. 2025 Aug;28(4):680-686. doi: 10.1111/ocr.12919. Epub 2025 Mar 29.
Genetic polymorphism of the α-actinin-3 (ACTN3) gene has an influence on the facial skeletal profile, with the activity of the α-actinins protein influencing the contractile properties of the masseteric muscles. This study examines the association between the ACTN3 rs1815739 polymorphism through a Stop Codon (changing 577RR to 577XX) resulting in variations in mandibular morphogenesis.
Two hundred and fifty subjects were categorised into three groups. The control group (Group 1) comprised 100 patients with skeletal Class I malocclusion. The experimental group (Group 2) had 150 subjects with skeletal Class II malocclusions and a retrognathic mandible, divided into two groups of 75 subjects each based on the ramal heights (short ramal height-Group 2a) and (long ramal height-Group 2b). Saliva samples of the subjects were analysed to identify the genotype of the rs1815739. Tissue samples were taken to quantify the mRNA expression in the different alleles studied.
Polymorphism of the ACTN3 gene with risk homozygous TT genotype was linked only to subjects with short ramal height. The highly variable polymorphic site exhibited a substitution of the ancestral allele cytosine (C) with thymine (T) inhibiting protein synthesis. The mRNA expression was also found to be reduced (p < 0.05) in the short ramal height group.
ACTN3 577XX polymorphism is more common among individuals with skeletal Class II malocclusion and short ramal height in the Dravidian population. It results in decreased protein expression in the masseteric muscle, which contributes to variations in sagittal and vertical facial dimensions.
α-辅肌动蛋白-3（ACTN3）基因的遗传多态性对面部骨骼轮廓有影响，α-辅肌动蛋白蛋白的活性会影响咬肌的收缩特性。本研究通过一个导致下颌形态发生变化的终止密码子（将577RR变为577XX）来检测ACTN3 rs1815739多态性之间的关联。
250名受试者被分为三组。对照组（第1组）包括100名骨骼I类错牙合患者。实验组（第2组）有150名骨骼II类错牙合且下颌后缩的受试者，根据升支高度分为两组，每组75名受试者（短升支高度-第2a组）和（长升支高度-第2b组）。分析受试者的唾液样本以确定rs1815739的基因型。采集组织样本以量化所研究的不同等位基因中的mRNA表达。
具有风险纯合TT基因型的ACTN3基因多态性仅与短升支高度的受试者相关。这个高度可变的多态性位点表现为祖先等位基因胞嘧啶（C）被胸腺嘧啶（T）取代，从而抑制蛋白质合成。在短升支高度组中还发现mRNA表达降低（p < 0.05）。
在达罗毗荼人群中，ACTN3 577XX多态性在骨骼II类错牙合且升支短的个体中更为常见。它导致咬肌中蛋白质表达减少，这有助于矢状和垂直面部尺寸的变化。
