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. 2024 Nov 26;9(1):bvae198.
doi: 10.1210/jendso/bvae198.

Oxytocin Receptor Polymorphism Is Associated With Sleep Apnea Symptoms

Hisanori Goto  1   2 , Yasuhiko Yamamoto  2 , Hiromasa Tsujiguchi  3   4 , Takehiro Sato  5 , Reina Yamamoto  1 , Yumie Takeshita  1 , Yujiro Nakano  1 , Takayuki Kannon  6 , Kazuyoshi Hosomichi  7 , Keita Suzuki  4 , Masaharu Nakamura  3 , Yasuhiro Kambayashi  3   8 , Jiaye Zhao  3 , Atsushi Asai  4 , Koji Katano  4 , Aya Ogawa  3 , Shinobu Fukushima  3 , Aki Shibata  3 , Fumihiko Suzuki  3   9 , Hirohito Tsuboi  3   10 , Akinori Hara  3   4 , Mitsuhiro Kometani  11 , Shigehiro Karashima  12 , Takashi Yoneda  11 , Atsushi Tajima  13 , Hiroyuki Nakamura  3   4 , Toshinari Takamura  1
Affiliations

Oxytocin Receptor Polymorphism Is Associated With Sleep Apnea Symptoms

Hisanori Goto et al. J Endocr Soc. .

Abstract

Context: 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.

Objective: In this study, we approached the contribution of the intrinsic oxytocin-oxytocin receptor (OXTR) system to OSA by genetic association analysis.

Methods: We analyzed the relationship between OXTR gene polymorphisms and sleep parameters using questionnaire data and sleep measurements in 305 Japanese participants. OSA symptoms were assessed in 225 of these individuals.

Results: The OXTR rs2254298 A allele was more frequent in those with OSA symptoms than in those without (P = .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 (P = .00045 and P = .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 (P = .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.

Conclusion: 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.

Keywords: genetic association study; obstructive sleep apnea; oxytocin; oxytocin receptor.

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Figures

Figure 1.
Figure 1.
Flowchart of inclusion and exclusion criteria for the study population.
Figure 2.
Figure 2.
Association of the plasma renin activity with OSA symptoms and rs2254298 genotype. (A) Comparison of plasma renin activity with (n = 173) and without (n = 29) OSA symptoms. (B) Comparison of plasma renin activity between rs2254298 A genotype (n = 33) and rs2254298 G genotype participants (n = 272) (recessive model). **P < .01; *P < .05; Abbreviation: ns, not significant.
Figure 3.
Figure 3.
Association of subjective sleep efficiency with OSA symptoms. A, Comparison of subjective sleep efficiency between participants with (n = 189) and without (n = 36) OSA symptoms for all participants. B, Comparison of subjective sleep efficiency between participants with (n = 16) and without (n = 7) OSA symptoms in the rs2254298 A genotype (recessive model). C, Comparison of subjective sleep efficiency between participants with (n = 173) and without (n = 29) OSA symptoms in the rs2254298 G genotype (recessive model). Abbreviation: ns, not significant.
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