Abstract: Background　In recent years，the prevalence of sleep disturbances during pregnancy has significantly increased due to rising social pressures and lifestyle changes. Studies suggest that circadian rhythm disruption may contribute to blood pressure dysregulation through mechanisms such as hypothalamic-pituitary-adrenal（HPA） axis activation and inflammatory responses. However，the interaction between environmental factors and genetic susceptibility remains unclear. Melatonin receptor 1B（MTNR1B），a key regulator of melatonin signaling，not only modulates circadian rhythms but also plays a critical role in maintaining placental vascular endothelial function. While MTNR1B polymorphisms are strongly associated with type 2 diabetes and insulin resistance，their role in gestational hypertension（GH） susceptibility remains undetermined. Objective　To investigate potential synergistic effects between maternal sleep quality during pregnancy and peripheral blood MTNR1B polymorphisms on GH development. Methods　This study enrolled 235 mid-pregnancy women receiving prenatal care at a provincial hospital in Gansu from March to December 2021，with 235 age-matched healthy pregnant women as controls. Assessments included the Pittsburgh Sleep Quality Index（PSQI），Hospital Anxiety and Depression Scale（HADS），and a pregnancy-specific sleep health questionnaire. Peripheral venous blood was collected before delivery，and improved multiplex ligation detection reaction（im-LDR） technology was employed for genotyping three MTNR1B single-nucleotide polymorphisms （rs3781638，rs10830963，rs3781637）. Logistic regression analyzed associations between late-pregnancy sleep parameters，MTNR1B polymorphisms，and GH risk，with multiplicative interaction models evaluating sleep-genotype interactions. Results　The genotype，allele type，dominant，and over-dominant genotypes comparison of the MTNR1B gene rs3781638 locus in the case group and the control group showed statistically significant differences（P<0.05）; there was no statistically significant difference in the comparison of the MTNR1B gene rs10830963 and rs3781637 loci between the two groups（P>0.05）. The results of the multivariate Logistics regression analysis showed that carrying the genotype GT（OR=1.88，95%CI=1.24-2.84），allele type T（OR=1.28，95%CI=1.02-1.71），dominant genotype GG+GT（OR=1.93，95%CI=1.29-2.89），and over-dominant genotype GT（OR=1.84，95%CI=1.22-2.72） are independent risk factors for the occurrence of GH; the interaction analysis results showed that carrying the TT genotype and coughing/snoring 1~2 times/week during nighttime sleep（OR=2.82，95%CI=1.36-5.84） and coughing/snoring ≥ 3 times/week（OR=2.21，95%CI=1.09-4.48） have 2.82 and 2.21 times the risk of GH compared to carrying the TT genotype and no coughing/snoring during nighttime sleep，respectively; compared to carrying the TT genotype and no coughing/snoring during nighttime sleep，carrying the GT+GG genotype，regardless of coughing/snoring during nighttime sleep，increases the risk of GH，with the highest risk of GH occurring when coughing/snoring ≥ 3 times/week（OR=4.90，95%CI=2.24-10.75）. Conclusion　The MTNR1B rs3781638（G>T） polymorphism may confer GH susceptibility and demonstrate synergistic effects with nocturnal snoring on GH pathogenesis.

Key words: Gestational hypertension, MTNR1B gene, Single nucleotide polymorphism, Sleep, Interaction

摘要： 背景　近年来，随着社会压力增加和生活方式改变，孕期睡眠问题发生率明显上升，研究发现睡眠节律失调可通过激活下丘脑-垂体-肾上腺轴、引发炎症反应等机制参与血压调节，但环境因素与遗传易感性的相互作用机制尚未明确。褪黑素受体基因1B（MTNR1B）作为褪黑素信号通路的关键调控因子，其编码的褪黑素受体基因1B不仅参与昼夜节律调节，更在胎盘血管内皮功能保持中发挥关键作用。MTNR1B基因多态性与2型糖尿病、胰岛素抵抗存在明显关联，但该基因多态性对妊娠期高血压易感性的调节作用仍不明确。目的　探讨孕妇孕期睡眠状况联合外周血MTNR1B基因多态性对妊娠期高血压（GH）发病是否存在协同效应。方法　纳入2021年3月—2021年12月在甘肃某省级医院产前检查的妊娠中期235例孕妇为研究对象，选取同期在该医院获得正常妊娠结局的235例健康孕产妇作为对照组，采用匹茨堡睡眠质量指数量表、医院焦虑抑郁量表、孕期睡眠相关健康因素调查问卷开展调查；收集对照组和病例组分娩前外周静脉血，采用改进型液相芯片检测技术（im-LDR）对MTNR1B基因的3个单核苷酸多态性位点（rs3781638、rs10830963、rs3781637）进行基因分型检测。使用多因素Logistics回归分析探讨孕晚期睡眠及MTNR1B基因多态性与GH发病的关联，并建立相乘交互作用模型，探讨睡眠-基因交互作用对GH的影响。结果　病例组和对照组MTNR1B基因rs3781638位点的基因型、等位基因型、显性和超显性基因型比较，差异均有统计学意义（P<0.05）；两组MTNR1B基因rs10830963、rs3781637位点相比，差异无统计学意义（P>0.05）。多因素Logistics回归分析结果显示，携带基因型GT（OR=1.88，95%CI=1.24~2.84）、等位基因型T（OR=1.28，95%CI=1.02~1.71）、显性基因型GG+GT（OR=1.93，95%CI=1.29~2.89）、超显性基因型GT（OR=1.84，95%CI=1.22~2.72）是发生GH的独立危险因素；交互作用分析结果显示，携带TT基因型且夜睡时咳嗽/打鼾1~2次/周（OR=2.82，95%CI=1.36~5.84）和咳嗽/打鼾≥3次/周（OR=2.21，95%CI=1.09~4.48）发生GH的风险分别是携带TT基因型且夜睡时无咳嗽/打鼾的2.82和2.21倍；与携带TT基因型且夜睡时无咳嗽/打鼾相比，携带GT+GG基因型，无论夜睡时有无咳嗽/打鼾，发生GH的风险均增加，其中夜睡时咳嗽/打鼾≥3次/周发生GH的风险最高（OR=4.90，95%CI=2.24~10.75）。结论　MTNR1B基因rs3781638（G>T）位点可能是GH的易感基因，且与夜睡打鼾对GH的发生发展存在协同效应。

关键词: 妊娠期高血压, MTNR1B 基因, 单核苷酸多态性, 孕期睡眠, 交互作用