title: Genome-wide association study of sensory disturbances in the inferior alveolar nerve after bilateral sagittal split ramus osteotomy.
abstract: BACKGROUND
  Bilateral sagittal split ramus osteotomy (BSSRO) is a common orthognatic surgical procedure. Sensory disturbances in the inferior alveolar nerve, including hypoesthesia and dysesthesia, are frequently observed after BSSRO, even without distinct nerve injury. The mechanisms that underlie individual differences in the vulnerability to sensory disturbances have not yet been elucidated.
  
  
  METHODS
  The present study investigated the relationships between genetic polymorphisms and the vulnerability to sensory disturbances after BSSRO in a genome-wide association study (GWAS). A total of 304 and 303 patients who underwent BSSRO were included in the analyses of hypoesthesia and dysesthesia, respectively. Hypoesthesia was evaluated using the tactile test 1 week after surgery. Dysesthesia was evaluated by interview 4 weeks after surgery. Whole-genome genotyping was conducted using Illumina BeadChips including approximately 300,000 polymorphism markers.
  
  
  RESULTS
  Hypoesthesia and dysesthesia occurred in 51 (16.8%) and 149 (49.2%) subjects, respectively. Significant associations were not observed between the clinical data (i.e., age, sex, body weight, body height, loss of blood volume, migration length of bone fragments, nerve exposure, duration of anesthesia, and duration of surgery) and the frequencies of hypoesthesia and dysesthesia. Significant associations were found between hypoesthesia and the rs502281 polymorphism (recessive model: combined χ² = 24.72, nominal P = 6.633 × 10⁻⁷), between hypoesthesia and the rs2063640 polymorphism (recessive model: combined χ² = 23.07, nominal P = 1.563 × 10⁻⁶), and between dysesthesia and the nonsynonymous rs2677879 polymorphism (trend model: combined χ² = 16.56, nominal P = 4.722 × 10⁻⁵; dominant model: combined χ² = 16.31, nominal P = 5.369 × 10⁻⁵). The rs502281 and rs2063640 polymorphisms were located in the flanking region of the ARID1B and ZPLD1 genes on chromosomes 6 and 3, whose official names are "AT rich interactive domain 1B (SWI1-like)" and "zona pellucida-like domain containing 1", respectively. The rs2677879 polymorphism is located in the METTL4 gene on chromosome 18, whose official name is "methyltransferase like 4".
  
  
  CONCLUSIONS
  The GWAS of sensory disturbances after BSSRO revealed associations between genetic polymorphisms located in the flanking region of the ARID1B and ZPLD1 genes and hypoesthesia and between a nonsynonymous genetic polymorphism in the METTL4 gene and dysesthesia.
authors.affiliation: Department of Oral Health and Clinical Science, Division of Dental Anesthesiology, Orofacial Pain Center, Suidoubashi Hospital, Tokyo Dental College, 2-9-18 Misaki-cho, Chiyoda-ku, Tokyo 101-0061, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kobayashi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nishizawa
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Takasaki
authors.forename: Shinya
authors.initials: S
authors.lastname: Kasai
authors.forename: Takashi
authors.initials: T
authors.lastname: Kakizawa
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Ikeda
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Fukuda
mesh_terms: D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D006987:Hypesthesia / Q000235:genetics* / Q000473:pathology; D008297:Male; D008334:Mandible / Q000601:surgery; D008340:Mandibular Nerve / Q000378:metabolism / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics*; D008780:Methyltransferases / Q000235:genetics*; D059229:Osteotomy, Sagittal Split Ramus / Q000009:adverse effects*; D010292:Paresthesia / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic; D014110:Touch; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C497837:ARID1B protein, human; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D014157:Transcription Factors; C533281:ZPLD1 protein, human; C586526:METTL4 protein, human; D008780:Methyltransferases