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gamma-Aminobutyric Acid (GABRA3)
May Be A Risk Factor For
Multiple Sclerosis

Radhika Gade-Andavolu, PhD; James P. MacMurray, PhD; Hezekiah Blake; Donn Muhleman, MS; Wallace Tourtellotte, MD; David E. Comings, MD
Arch Neurol April,1998;55:513-516
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 Multiple Sclerosis.

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<.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.



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