Identification of a naturally occurring Pro385-Ser385 substitution in the GABA(A) receptor α6 subunit gene in alcoholics and healthy volunteers

N. Iwata, M. Virkkunen, D. Goldman

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

In the rat, variation in alcohol and benzodiazepine sensitivity has been correlated with an inherited variant of the GABA(A)α6 receptor. Our goal was to identify polymorphisms in the human GABA(A)α6 receptor gene and determine whether a variant of the receptor is associated with alcoholism. The GABA(A)α6 receptor gene coding region was screened in 80 unrelated patients with alcoholism using single strand conformational polymorphism analysis. For rapid genotyping, a Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) assay was developed. A relatively abundant amino acid substitution and three synonymous DNA substitutions were detected. The synonymous variants, 35A > G, 665A > G, and 1031G > C had rare-allele frequencies of 0.25, 0.02, and 0.47, respectively. The Pro385Ser substitution is located in the second intracellular domain of the receptor adjacent to a putative phosphorylation site. Pro385Ser has rarer allele frequencies of 3.3% and 4.8% in 196 Finnish alcoholic patients and 189 controls, respectively (P = NS). A naturally occurring non-conservative Pro385Ser was detected in the GABA(A)α6 receptor. The variant is not associated with alcoholism.

Original languageEnglish
Pages (from-to)316-319
Number of pages4
JournalMolecular Psychiatry
Volume5
Issue number3
DOIs
Publication statusPublished - 01-01-2000

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GABA-A Receptors
Alcoholics
Healthy Volunteers
Alcoholism
Gene Frequency
Genes
Amino Acid Substitution
Benzodiazepines
Restriction Fragment Length Polymorphisms
Phosphorylation
Alcohols
Polymerase Chain Reaction
DNA

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

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abstract = "In the rat, variation in alcohol and benzodiazepine sensitivity has been correlated with an inherited variant of the GABA(A)α6 receptor. Our goal was to identify polymorphisms in the human GABA(A)α6 receptor gene and determine whether a variant of the receptor is associated with alcoholism. The GABA(A)α6 receptor gene coding region was screened in 80 unrelated patients with alcoholism using single strand conformational polymorphism analysis. For rapid genotyping, a Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) assay was developed. A relatively abundant amino acid substitution and three synonymous DNA substitutions were detected. The synonymous variants, 35A > G, 665A > G, and 1031G > C had rare-allele frequencies of 0.25, 0.02, and 0.47, respectively. The Pro385Ser substitution is located in the second intracellular domain of the receptor adjacent to a putative phosphorylation site. Pro385Ser has rarer allele frequencies of 3.3{\%} and 4.8{\%} in 196 Finnish alcoholic patients and 189 controls, respectively (P = NS). A naturally occurring non-conservative Pro385Ser was detected in the GABA(A)α6 receptor. The variant is not associated with alcoholism.",
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Identification of a naturally occurring Pro385-Ser385 substitution in the GABA(A) receptor α6 subunit gene in alcoholics and healthy volunteers. / Iwata, N.; Virkkunen, M.; Goldman, D.

In: Molecular Psychiatry, Vol. 5, No. 3, 01.01.2000, p. 316-319.

Research output: Contribution to journalArticle

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