Alleic Variants of Human Melatonin 1a Receptor: Function and Prevalence in Subjects With Circadian Rhythm Sleep Disorders

Biochem Biophys Res Commun. 1999 Sep 7;262(3):832-7. doi: 10.1006/bbrc.1999.1308.

Abstract

The human melatonin 1a (hMella) receptor gene was screened for mutations using genomic DNA samples from patients with circadian rhythm sleep disorders and control subjects by single strand conformational polymorphism analysis (SSCP). We found seven mutations, two of which predict amino acid changes R54W and A157V, respectively. The prevalence of the R54W variant and that of the A157V variant were several times more common in non-24-h sleep-wake syndrome subjects than among control subjects, although the incidence was not significant in our study group. When expressed in COS-7 cells, the R54W mutant receptor exhibited significantly reduced B(max) and slightly enhanced affinity (reduced K(d)) compared to the wild type receptor, while the A157V variant receptor showed similar binding characteristics to the wild type. The identification of variants in the hMella receptor will provide a useful tool for analyzing genetic predisposition toward various diseases related to melatonin function and to clarify the physiological role of melatonin receptors in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Substitution
  • Base Sequence
  • Circadian Rhythm*
  • Cloning, Molecular
  • DNA Primers
  • Genetic Variation*
  • Humans
  • Melatonin / physiology
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Mutation, Missense*
  • Point Mutation*
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / metabolism
  • Receptors, Cytoplasmic and Nuclear / chemistry
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, Melatonin
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Sleep Wake Disorders / genetics*
  • Sleep Wake Disorders / physiopathology

Substances

  • DNA Primers
  • Receptors, Cell Surface
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Melatonin
  • Recombinant Proteins
  • Melatonin

Associated data

  • GENBANK/AB029932
  • GENBANK/AB029933