Genetic variability of arylalkylamine-N-acetyl-transferase (AA-NAT) gene and human sleep/wake pattern

Chronobiol Int. 2004 Mar;21(2):229-37. doi: 10.1081/cbi-120037822.

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.

MeSH terms

  • Adolescent
  • Adult
  • Arylamine N-Acetyltransferase / genetics*
  • Base Sequence
  • Circadian Rhythm / physiology*
  • Female
  • Genetic Variation*
  • Humans
  • Male
  • Melatonin / metabolism
  • Middle Aged
  • Promoter Regions, Genetic
  • Sleep / genetics
  • Sleep / physiology*
  • Statistics as Topic
  • Surveys and Questionnaires
  • Wakefulness / genetics
  • Wakefulness / physiology*

Substances

  • Arylamine N-Acetyltransferase
  • Melatonin