Abstract
BackgroundBilateral 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.MethodsThe 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.ResultsHypoesthesia 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”.ConclusionsThe 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.
Highlights
Bilateral sagittal split ramus osteotomy (BSSRO) is a common orthognatic surgical procedure
Logistic regression analysis revealed no significant associations between the clinical data and frequency of hypoesthesia or dysesthesia after BSSRO
After filtering the markers by genotype call frequency, “Cluster sep”, and minor allele frequencies in the first quality control assessment of the genotyping data, 243,501 markers were selected. These merged genotype data from five different BeadChips consisted of single nucleotide polymorphism (SNP) markers on the autosome or sex chromosome, and no mitochondrial marker was included
Summary
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. Sensory disturbances, including hypoesthesia and dysesthesia, often appear as a prodromal symptom of neuropathic pain. Sensory disturbances in the inferior alveolar nerve, including hypoesthesia and dysesthesia, are frequently observed in the lower lip and mental area after BSSRO, even without distinct nerve injury. Considering that almost all patients who undergo BSSRO are young and healthy and the degree of surgical invasiveness, surgical site, and surgical procedures are highly consistent across cases, environmental factors appear to have relatively little impact on individual differences in the vulnerability to sensory disturbances or neuropathic pain after BSSRO
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