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    ENPP1 AND ESR1 GENOTYPE ASSOCIATE WITH CRANIOFACIAL ASYMMETRY AND SEVERITY OF TMD

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    Genre
    Thesis/Dissertation
    Date
    2018
    Author
    Chung, Ki Yoon
    Advisor
    Sciote, James J.
    Committee member
    Godel, Jeffrey H.
    Spannhake, Elizabeth
    Department
    Oral Biology
    Subject
    Dentistry
    Permanent link to this record
    http://hdl.handle.net/20.500.12613/974
    
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    DOI
    http://dx.doi.org/10.34944/dspace/956
    Abstract
    Introduction: There are many approaches for classification of skeletal asymmetry using either PA cephalograms or SMV radiographs; however, there is no universally accepted one. We developed a new classification system to remove much of the previous diagnostic uncertainty that is also useful in genotyping single nucleotide polymorphisms (SNPs) associated with asymmetry. Also, we investigated whether ACTN3, ENPP1, ESR1, PITX1, and PITX2 genes which contribute to sagittal and vertical malocclusions also contribute to facial asymmetries and temporomandibular disorders (TMD) before and after orthodontic and orthognathic surgery treatment. Methods: One hundred seventy-four patients with a dentofacial deformity were diagnosed as symmetric or subdivided into 4 asymmetric groups according to posteroanterior cephalometric measurements. 13 SNPs in ACTN3, ENPP1, ESR1, PITX,1 and PITX2 were selected for genotyping to determine whether specific allelic variants were overrepresented in subjects with malocclusion subclassifications. TMD examination diagnosis and jaw pain and function (JPF) questionnaires assessed the presence and severity of TMD. Results: Fifty-two percent of the patients were symmetric, and 48% were asymmetric. The asymmetry classification demonstrated significant cephalometric differences between the symmetric and asymmetric groups, and across the 4 asymmetric subtypes: group 1, mandibular body asymmetry; group 2, ramus asymmetry; group 3, atypical asymmetry; and group 4, C-shaped asymmetry. ENPP1 SNP-rs6569759 was associated with group 1 (p=0.004), and rs858339 was associated with group 3 (p=0.002). ESR1 SNP-rs164321 was associated with group 4 (p=0.019). Diagnoses of disc displacement with reduction, masticatory muscle myalgia, and arthralgia were highly prevalent in the asymmetry groups, and all had strong statistical associations with ENPP1 rs858339. The average JPF scores for asymmetric subjects before surgery (JPF, 7) were significantly higher than for symmetric subjects (JPF, 2). Patients in group 3 had the highest preoperative JPF scores, and groups 2 and 3 were most likely to be cured of TMD 1 year after treatment. Conclusions: 1. A new posteroanterior cephalometric analysis using 6 measurements to detect differences in facial sides has been developed to distinguish 4 main classifications of asymmetry that are common in patients with dentofacial deformity. 2. TMD prevalence is much higher in patients with asymmetry compared with patients with dentofacial deformity without asymmetry. a. The most common TMD presentations were disc displacement with reduction, masticatory muscle myalgia, and arthralgia. b. Two of the 4 asymmetry groups had both high positive diagnoses for TMD and subjective patient reporting of symptoms. 3. SNP genotype rs6569759 in ENPP1 was associated with asymmetry group 1, and rs858339 was associated with asymmetry group 3. 4. SNP genotype rs1643821 in ESR1 was associated with asymmetry group 4. rs3020318 in ESR1 was associated with PC1 and PC2, which relate to maxillary canting and menton deviation. 5. SNP genotype rs858339 in ENPP1 was associated with disc displacement with reduction, masticatory muscle myalgia, and arthralgia. 6. Orthodontic and orthognathic treatment of asymmetry alleviates TMD symptoms for at least 1 year into retention in most patients.
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