Genetic variability of arylalkylamine-N-acetyl-transferase (AA-NAT) gene and human sleep/wake pattern
Abstract
The cyclic production and secretion of melatonin has been associated with the sleep/wake cycle as well as other circadian rhythms. Since arylalkylamine-N-acetyl-transferase (AA-NAT) is the rate-limiting enzyme responsible for the production of melatonin, it has been postulated to determine the circadian oscillations of melatonin. Genetic variability of the AA-NAT gene may therefore potentially influence sleep patterns in the normal population. In this study, a sleep pattern survey was performed in 210 students. Five subjects with early sleep onset time and long sleep duration (early/long sleepers), and 5 subjects with late sleep onset time and short sleep duration (late/short sleepers) were identified for genetic studies. All 10 subjects had identical sequences throughout the coding regions of the AA-NAT gene. In the promoter region, a -263G/C (relative to the transcription start site) single nucleotide polymorphism (SNP) was observed in 4 of the 5 late/short sleepers, but in only 1 of 5 early/long sleepers. The -263G/C SNP may therefore be an important determinant of the late/short sleep pattern.
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