抄録
Some people cannot adjust their sleep-wake cycle to socially-desired time schedule, called circadian rhythm sleep disorders (CRSD). Recent studies revealed that functional variations in human clock genes confer susceptibility to CRDS, such as delayed sleep phase syndrome (DSPS), advanced sleep phase syndrome (ASPS), and non-24-hour sleep-wake syndrome (N-24). Missense variations in Period2 (Per2) gene and Casein kinase1 delta (CK1δ) gene, each of which reduces phosphorylation of PER protein, reportedly cause familial ASPS. We have already reported that a missense variation in Per3 gene, which presumably affect phosphorylation of PER3 protein, increases the risk for DSPS and that a missense variation in CK1ε gene, which increases the kinase activity, plays a protective role in the development of DSPS. It is intriguing that all of the CRDS-susceptibility variations found so far, as described above, seem to alter the phosphorylatrion of PER proteins.Functional clock gene variations are also observed in apparently normal subjects and likely to induce interindividual differences in circadian period. Comprehensive genetic analysis for variations of human circadian rhythmicity will make it possible to fully understand the characteristics of each indivisual's internal clock, leading to alleviation of health injury and economic loss induced by sleep disorders or maladaptation to socially-desired time schedule, with which a large number of people are afflicted in the modern society. [J Physiol Sci. 2006;56 Suppl:S16]
