title: Association between the gamma-aminobutyric acid A3 receptor gene and multiple sclerosis.
abstract: BACKGROUND
  In a prior study we observed an association between the dopamine D2 receptor gene (DRD2) and the age of onset and/or diagnosis of multiple sclerosis (MS). We hypothesized that this effect was mediated through the dopaminergic control of the release of prolactin, a modulator of immune response. Since gamma-aminobutyric acid also modulates the release of prolactin, we examined the possible association between alleles of the GABRA3 (gamma-aminobutyric acid A3 receptor) gene and MS.
  
  
  METHODS
  We examined the GABRA3 alleles of 189 subjects with MS who died of their disease. They were divided into test group 1 (n=64) and retest group 2 (n=56). Each group had a separate set of controls (group 1, n=109; group 2, n=430). All subjects were white. All were tested at a dinucleotide cytosine-adenosine repeat polymorphism with 6 alleles representing 11 to 16 repeats.
  
  
  RESULTS
  In the first group there was a significant difference in the frequency of the GABRA3 alleles (P<.002), with the most notable difference being an increase in the frequency of the 16-repeat allele in subjects with MS and a relative decrease in the other alleles. In the replication group there was again a significant difference in the distribution of the GABRA3 alleles (P<.001), and again the greatest difference was an increase in the frequency of the 16-repeat allele in subjects with MS. For both groups combined, a significant difference in the frequency of the 16-repeat allele was noted (chi2=46.30; P<.001).
  
  
  CONCLUSIONS
  These results suggest the GABRA3 gene may be a risk factor for MS. As with the DRD2 gene, the effect may be mediated through its regulation of prolactin release.
authors.affiliation: Department of Medical Genetics, City of Hope Medical Center, Duarte, Calif 91910, USA.
authors.forename: R
authors.initials: R
authors.lastname: Gade-Andavolu
authors.forename: J P
authors.initials: JP
authors.lastname: MacMurray
authors.forename: H
authors.initials: H
authors.lastname: Blake
authors.forename: D
authors.initials: D
authors.lastname: Muhleman
authors.forename: W
authors.initials: W
authors.lastname: Tourtellotte
authors.forename: D E
authors.initials: DE
authors.lastname: Comings
mesh_terms: D000483:Alleles; D016009:Chi-Square Distribution; D016207:Cytokines / Q000378:metabolism; D005260:Female; D008040:Genetic Linkage; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics*; D011388:Prolactin / Q000502:physiology*; D011963:Receptors, GABA-A / Q000235:genetics*; D012307:Risk Factors; D018433:Twin Studies as Topic; D014960:X Chromosome; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D016207:Cytokines; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D011388:Prolactin; D005968:Glutamate Decarboxylase