Laboratory of Molecular Chronobiology, Federal University of Alagoas (UFAL), Alagoas, Brazil.
Laboratory of Pharmacology and Immunity, Federal University of Alagoas (UFAL), Alagoas, Brazil.
Sleep Med. 2019 Jan;53:106-114. doi: 10.1016/j.sleep.2018.09.023. Epub 2018 Oct 13.
Melatonin modulates the master circadian clock through the activation of G-protein-coupled receptors MT1 and MT2. It is presumed, therefore, that genetic variations in melatonin receptors can affect both sleep and circadian phase. We investigated whether the -1193T > C (rs4753426) polymorphism in the promoter of MT2 receptor gene (MTNR1B) is associated with diurnal preference and sleep habits. This polymorphism was previously associated with sunshine duration, suggesting a role in circadian entrainment.
A total of 814 subjects who completed the Morningness-Eveningness and the Munich Chronotype questionnaires were genotyped for the selected polymorphism. Linear and multinomial regression were performed to test the interaction between gene variants and diurnal preference/sleep habits.
The -1193C variant was associated with the extreme morningness phenotype in a codominant model (C/C vs. T/T), recessive model (C/C + C/T vs. T/T) and alleles (C vs. T). A negative correlation was found between -1193C alleles and social jetlag scores. The frequency of -1193T allele was higher in the group that stay in bed more than 8 h/night compared to the group that stay in bed less than 8 h/night on weekends.
To the best of our knowledge, these data provide the first insights into the role of MTNR1B gene in the regulation of sleep, biological rhythms, and entrainment in humans.
褪黑素通过激活 G 蛋白偶联受体 MT1 和 MT2 来调节主生物钟。因此，可以假定褪黑素受体的遗传变异会影响睡眠和昼夜节律相位。我们研究了 MT2 受体基因（MTNR1B）启动子中的-1193T>C（rs4753426）多态性是否与昼夜偏好和睡眠习惯有关。该多态性先前与阳光持续时间有关，表明其在昼夜节律同步中起作用。
共有 814 名完成了Morningness-Eveningness 和慕尼黑睡眠类型问卷的受试者接受了所选多态性的基因分型。进行线性和多项回归分析，以测试基因变异与昼夜偏好/睡眠习惯之间的相互作用。
-1193C 变体在显性模型（C/C 与 T/T）、隐性模型（C/C+C/T 与 T/T）和等位基因（C 与 T）中与极端早发性表型相关。在周末，与卧床时间少于 8 小时/夜的组相比，-1193C 等位基因与社会时差评分呈负相关。与卧床时间超过 8 小时/夜的组相比，-1193T 等位基因的频率在周末卧床时间超过 8 小时/夜的组中更高。
据我们所知，这些数据首次提供了关于 MTNR1B 基因在人类睡眠、生物节律和同步调节中的作用的见解。
