Goto Hisanori, Yamamoto Yasuhiko, Tsujiguchi Hiromasa, Sato Takehiro, Yamamoto Reina, Takeshita Yumie, Nakano Yujiro, Kannon Takayuki, Hosomichi Kazuyoshi, Suzuki Keita, Nakamura Masaharu, Kambayashi Yasuhiro, Zhao Jiaye, Asai Atsushi, Katano Koji, Ogawa Aya, Fukushima Shinobu, Shibata Aki, Suzuki Fumihiko, Tsuboi Hirohito, Hara Akinori, Kometani Mitsuhiro, Karashima Shigehiro, Yoneda Takashi, Tajima Atsushi, Nakamura Hiroyuki, Takamura Toshinari
Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa 920-8640, Japan.
Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa 920-8640, Japan.
J Endocr Soc. 2024 Nov 26;9(1):bvae198. doi: 10.1210/jendso/bvae198.
Oxytocin supplementation improves obstructive sleep apnea (OSA), and animal studies suggest involvement of oxytocin in respiratory control. However, the relationship between endogenous oxytocin signaling and human sleep status remains undetermined.
In this study, we approached the contribution of the intrinsic oxytocin-oxytocin receptor (OXTR) system to OSA by genetic association analysis.
We analyzed the relationship between gene polymorphisms and sleep parameters using questionnaire data and sleep measurements in 305 Japanese participants. OSA symptoms were assessed in 225 of these individuals.
The OXTR rs2254298 A allele was more frequent in those with OSA symptoms than in those without ( = .0087). Although total scores on the Pittsburgh Sleep Quality Index questionnaire did not differ between the genotypes, breathlessness and snoring symptoms associated with OSA were significantly more frequent in individuals with rs2254298 A genotype ( = .00045 and = .0089 for recessive models, respectively) than the G genotype. A multivariable analysis confirmed these genotype-phenotype associations even after adjusting for age, sex, and body mass index in a sensitivity analysis. Furthermore, objective sleep efficiency measured by actigraph was not significantly different between genotypes; however, subjective sleep efficiency was significantly lower in the rs2254298 A genotype ( = .013) compared with the G genotype. The frequency of the A allele is higher in East Asians, which may contribute to their lean OSA phenotype.
The OXTR gene may contribute to OSA symptoms via the respiratory control system, although it could be in linkage disequilibrium with a true causal gene.
补充催产素可改善阻塞性睡眠呼吸暂停（OSA），动物研究表明催产素参与呼吸控制。然而，内源性催产素信号与人类睡眠状态之间的关系仍未确定。
在本研究中，我们通过基因关联分析探讨了内源性催产素 - 催产素受体（OXTR）系统对OSA的作用。
我们使用305名日本参与者的问卷数据和睡眠测量结果分析了基因多态性与睡眠参数之间的关系。其中225人评估了OSA症状。
OXTR rs2254298 A等位基因在有OSA症状的人群中比没有症状的人群中更常见（P = 0.0087）。尽管匹兹堡睡眠质量指数问卷的总分在不同基因型之间没有差异，但rs2254298 A基因型个体中与OSA相关的呼吸急促和打鼾症状比G基因型个体更频繁（隐性模型分别为P = 0.00045和P = 0.0089）。多变量分析在敏感性分析中调整了年龄、性别和体重指数后，仍证实了这些基因型 - 表型关联。此外，通过活动记录仪测量的客观睡眠效率在不同基因型之间没有显著差异；然而，rs2254298 A基因型的主观睡眠效率与G基因型相比显著更低（P = 0.013）。A等位基因在东亚人中的频率更高，这可能导致他们出现瘦型OSA表型。
OXTR基因可能通过呼吸系统导致OSA症状，尽管它可能与真正的致病基因处于连锁不平衡状态。
