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Molecular Pain
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Genome-wide Association Study of Sensory Disturbances in the Inferior Alveolar Nerve after Bilateral Sagittal Split Ramus Osteotomy

Authors: Kobayashi, Daisuke; Nishizawa, Daisuke; Takasaki, Yoshito; Kasai, Shinya; Kakizawa, Takashi; Ikeda, Kazutaka; Fukuda, Ken-ichi;

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 X2 = 24.72, nominal P = 6.633 × 10−7), between hypoesthesia and the rs2063640 polymorphism (recessive model: combined X2 = 23.07, nominal P = 1.563 × 10−6), and between dysesthesia and the nonsynonymous rs2677879 polymorphism (trend model: combined X2 = 16.56, nomina P = 4.722 × 10−5; dominant model: combined X2 = 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 (SW11 -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.

Keywords

Male, Polymorphism, Genetic, Genotype, Research, Mandibular Nerve, Osteotomy, Sagittal Split Ramus, Membrane Proteins, Mandible, Methyltransferases, DNA-Binding Proteins, Hypesthesia, Anesthesiology and Pain Medicine, Touch, Molecular Medicine, Humans, Female, Paresthesia, Genome-Wide Association Study, Transcription Factors

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
11
Top 10%
Average
Average
Green
gold