Characterization of the genetic variability of human arylalklamine-N-acetyltransferase (AA-NAT) and its potential effects on melatonin production and the sleep pattern

The human sleep/wake cycle is characterized by a circadian rhythm of circulating melatonin levels, which has been attributed to the cyclic expression of its biosynthetic rate-limiting enzyme, arylalkylamine-N-acetyl-transferase (AA-NAT). Genetic variability of the AA-NAT gene may therefore potentially influence sleep patterns in normal population and account for the widely reported inter-individual variability of melatonin production. In this project, an initial sleep pattern study performed in university students identified a SNP in the promoter sequence that was apparently associated with extremes in sleep pattern. The possible association between overnight melatonin excretion and the -263G/C SNP was investigated through a second population study. Although the frequency of this SNP was relatively common, it had only a small and statistically insignificant effect on the overnight melatonin excretion. However, in vitro transfection experiments demonstrated that this SNP significantly disrupted basal promoter function, but appeared not to affect the in vitro responsiveness to cAMP-Ca2+ treatment.

Author dc:creator

• WANG YING

• 6-hydroxymelatonin sulfate (6-OHMS), arylalkylamine N-acetyltransferase (AA-NAT), melatonin, polymorphism, promoter, sleep pattern.