Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland.
PLoS One. 2010 Apr 2;5(4):e10007. doi: 10.1371/journal.pone.0010007.
Circadian clocks guide the metabolic, cell-division, sleep-wake, circadian and seasonal cycles. Abnormalities in these clocks may be a health hazard. Circadian clock gene polymorphisms have been linked to sleep, mood and metabolic disorders. Our study aimed to examine polymorphisms in four key circadian clock genes in relation to seasonal variation, reproduction and well-being in a sample that was representative of the general population, aged 30 and over, living in Finland.
METHODOLOGY/PRINCIPAL FINDINGS: Single-nucleotide polymorphisms in the ARNTL, ARNTL2, CLOCK and NPAS2 genes were genotyped in 511 individuals. 19 variants were analyzed in relation to 31 phenotypes that were assessed in a health interview and examination study. With respect to reproduction, women with ARNTL rs2278749 TT genotype had more miscarriages and pregnancies, while NPAS2 rs11673746 T carriers had fewer miscarriages. NPAS2 rs2305160 A allele carriers had lower Global Seasonality Scores, a sum score of six items i.e. seasonal variation of sleep length, social activity, mood, weight, appetite and energy level. Furthermore, carriers of A allele at NPAS2 rs6725296 had greater loadings on the metabolic factor (weight and appetite) of the global seasonality score, whereas individuals with ARNTL rs6290035 TT genotype experienced less seasonal variation of energy level.
CONCLUSIONS/SIGNIFICANCE: ARNTL and NPAS2 gene variants were associated with reproduction and with seasonal variation. Earlier findings have linked ARNTL to infertility in mice, but this is the first time when any polymorphism of these genes is linked to fertility in humans.
昼夜节律钟指导代谢、细胞分裂、睡眠-觉醒、昼夜和季节性周期。这些时钟的异常可能是健康的危害。昼夜节律钟基因多态性与睡眠、情绪和代谢紊乱有关。我们的研究旨在研究四个关键的昼夜节律钟基因的多态性与代表一般人群的芬兰 30 岁及以上人群的季节性变化、生殖和健康的关系。
方法/主要发现：在 511 名个体中，对 ARNTL、ARNTL2、CLOCK 和 NPAS2 基因中的单核苷酸多态性进行了基因分型。分析了 19 个变体与健康访谈和体检研究中评估的 31 个表型之间的关系。关于生殖，ARNTL rs2278749 TT 基因型的女性流产和妊娠次数较多，而 NPAS2 rs11673746 T 携带者流产次数较少。NPAS2 rs2305160 A 等位基因携带者的全球季节性评分较低，这是六个项目的总和，即睡眠长度、社会活动、情绪、体重、食欲和能量水平的季节性变化。此外，NPAS2 rs6725296 上的 A 等位基因携带者的全球季节性评分的代谢因子（体重和食欲）的负荷更大，而 ARNTL rs6290035 TT 基因型的个体经历的能量水平季节性变化较小。
结论/意义：ARNTL 和 NPAS2 基因变体与生殖和季节性变化有关。以前的研究发现 ARNTL 与小鼠的不育有关，但这是这些基因的任何多态性与人类生育能力有关的首次报道。
