Association Between the γ-Aminobutyric Acid A3 Receptor Gene and Multiple Sclerosis

Background In a prior study we observed an association between the dopamine D 2 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 γ-aminobutyric acid also modulates the release of prolactin, we examined the possible association between alleles of the GABRA3 (γ-aminobutyric acid A 3 receptor) gene and MS. Design 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 GABRA3 alleles ( P 2 =46.30; P 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.