Genetic variability of arylalkylamine-N-acetyl-transferase (AA-NAT) gene and human sleep/wake pattern.
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.
Department of Pharmacology, Faculty of Medicine, National University of Singapore, Singapore.
Grace Ying
GY
Wang
Caroline Guat Lay
CG
Lee
Edmund Jon Deoon
EJ
Lee
D000293:Adolescent; D000328:Adult; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D001483:Base Sequence; D002940:Circadian Rhythm / Q000502:physiology*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008550:Melatonin / Q000378:metabolism; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012890:Sleep / Q000235:genetics / Q000502:physiology*; D013223:Statistics as Topic; D011795:Surveys and Questionnaires; D014851:Wakefulness / Q000235:genetics / Q000502:physiology*
D001191:Arylamine N-Acetyltransferase; D008550:Melatonin