Selective genotyping for the role of 5-HT(2A), 5-HT(2C), and GABA(α6) receptors and the serotonin transporter in the level of response to alcohol: A pilot study

Marc A. Schuckit, Chiara Mazzanti, Tom L. Smith, Umbereen Ahmed, Marta Radel, Nakao Iwata, David Goldman

Research output: Contribution to journalArticle

203 Citations (Scopus)

Abstract

Background: The vulnerability to alcohol dependence appears to be genetically influenced through a variety of mechanisms. One potentially genetically mediated channel may be a low level of response (LR) to alcohol, which has been seen in children of alcoholics and noted to predict future alcohol abuse and dependence. This pilot study uses a case and control genetic association approach to evaluate the possible role of five genotypes in both LR and alcoholism in informative subgroups of men with high and low LR scores documented 15 years earlier. Methods: As part of a larger study, 41 men, about 39 years old, were selected from among the first 113, completed 15-year follow-ups in a prospective study. The 17 subjects whose LRs at age 20 were in the lower third were compared on five polymorphisms of four genes with 24 men whose reactions to alcohol had been above the median. Results: The 14 men with the LL genotype of the serotonin transporter (5-HTT) polymorphism and the seven with the Pro/Ser genotype of the GABA(Aα6) polymorphism had demonstrated lower LR scores at about age 20, and had significantly higher proportions of alcoholics than the other genotypes for those loci. All four subjects with combined LL and Pro/Ser genotypes had developed alcoholism and demonstrated the lowest LR scores overall. There was no evidence that two polymorphisms of the 5-HT(2A) receptor gene and one of the 5-HT(2C) receptor gene were related to LR or alcoholism in this sample. Conclusions: These results are consistent with animal and human studies suggesting a possible role for genetic variation in the GABA(Aα6) and the serotonin transporter in the reaction to alcohol and the alcoholism risk.

Original languageEnglish
Pages (from-to)647-651
Number of pages5
JournalBiological Psychiatry
Volume45
Issue number5
DOIs
Publication statusPublished - 01-03-1999
Externally publishedYes

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Serotonin Plasma Membrane Transport Proteins
GABA Receptors
Alcoholism
Serotonin
Alcohols
Genotype
Alcoholics
gamma-Aminobutyric Acid
Receptor, Serotonin, 5-HT2C
Genes
Receptor, Serotonin, 5-HT2A
Prospective Studies

All Science Journal Classification (ASJC) codes

  • Biological Psychiatry

Cite this

Schuckit, Marc A. ; Mazzanti, Chiara ; Smith, Tom L. ; Ahmed, Umbereen ; Radel, Marta ; Iwata, Nakao ; Goldman, David. / Selective genotyping for the role of 5-HT(2A), 5-HT(2C), and GABA(α6) receptors and the serotonin transporter in the level of response to alcohol : A pilot study. In: Biological Psychiatry. 1999 ; Vol. 45, No. 5. pp. 647-651.
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abstract = "Background: The vulnerability to alcohol dependence appears to be genetically influenced through a variety of mechanisms. One potentially genetically mediated channel may be a low level of response (LR) to alcohol, which has been seen in children of alcoholics and noted to predict future alcohol abuse and dependence. This pilot study uses a case and control genetic association approach to evaluate the possible role of five genotypes in both LR and alcoholism in informative subgroups of men with high and low LR scores documented 15 years earlier. Methods: As part of a larger study, 41 men, about 39 years old, were selected from among the first 113, completed 15-year follow-ups in a prospective study. The 17 subjects whose LRs at age 20 were in the lower third were compared on five polymorphisms of four genes with 24 men whose reactions to alcohol had been above the median. Results: The 14 men with the LL genotype of the serotonin transporter (5-HTT) polymorphism and the seven with the Pro/Ser genotype of the GABA(Aα6) polymorphism had demonstrated lower LR scores at about age 20, and had significantly higher proportions of alcoholics than the other genotypes for those loci. All four subjects with combined LL and Pro/Ser genotypes had developed alcoholism and demonstrated the lowest LR scores overall. There was no evidence that two polymorphisms of the 5-HT(2A) receptor gene and one of the 5-HT(2C) receptor gene were related to LR or alcoholism in this sample. Conclusions: These results are consistent with animal and human studies suggesting a possible role for genetic variation in the GABA(Aα6) and the serotonin transporter in the reaction to alcohol and the alcoholism risk.",
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Selective genotyping for the role of 5-HT(2A), 5-HT(2C), and GABA(α6) receptors and the serotonin transporter in the level of response to alcohol : A pilot study. / Schuckit, Marc A.; Mazzanti, Chiara; Smith, Tom L.; Ahmed, Umbereen; Radel, Marta; Iwata, Nakao; Goldman, David.

In: Biological Psychiatry, Vol. 45, No. 5, 01.03.1999, p. 647-651.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Selective genotyping for the role of 5-HT(2A), 5-HT(2C), and GABA(α6) receptors and the serotonin transporter in the level of response to alcohol

T2 - A pilot study

AU - Schuckit, Marc A.

AU - Mazzanti, Chiara

AU - Smith, Tom L.

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AU - Radel, Marta

AU - Iwata, Nakao

AU - Goldman, David

PY - 1999/3/1

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N2 - Background: The vulnerability to alcohol dependence appears to be genetically influenced through a variety of mechanisms. One potentially genetically mediated channel may be a low level of response (LR) to alcohol, which has been seen in children of alcoholics and noted to predict future alcohol abuse and dependence. This pilot study uses a case and control genetic association approach to evaluate the possible role of five genotypes in both LR and alcoholism in informative subgroups of men with high and low LR scores documented 15 years earlier. Methods: As part of a larger study, 41 men, about 39 years old, were selected from among the first 113, completed 15-year follow-ups in a prospective study. The 17 subjects whose LRs at age 20 were in the lower third were compared on five polymorphisms of four genes with 24 men whose reactions to alcohol had been above the median. Results: The 14 men with the LL genotype of the serotonin transporter (5-HTT) polymorphism and the seven with the Pro/Ser genotype of the GABA(Aα6) polymorphism had demonstrated lower LR scores at about age 20, and had significantly higher proportions of alcoholics than the other genotypes for those loci. All four subjects with combined LL and Pro/Ser genotypes had developed alcoholism and demonstrated the lowest LR scores overall. There was no evidence that two polymorphisms of the 5-HT(2A) receptor gene and one of the 5-HT(2C) receptor gene were related to LR or alcoholism in this sample. Conclusions: These results are consistent with animal and human studies suggesting a possible role for genetic variation in the GABA(Aα6) and the serotonin transporter in the reaction to alcohol and the alcoholism risk.

AB - Background: The vulnerability to alcohol dependence appears to be genetically influenced through a variety of mechanisms. One potentially genetically mediated channel may be a low level of response (LR) to alcohol, which has been seen in children of alcoholics and noted to predict future alcohol abuse and dependence. This pilot study uses a case and control genetic association approach to evaluate the possible role of five genotypes in both LR and alcoholism in informative subgroups of men with high and low LR scores documented 15 years earlier. Methods: As part of a larger study, 41 men, about 39 years old, were selected from among the first 113, completed 15-year follow-ups in a prospective study. The 17 subjects whose LRs at age 20 were in the lower third were compared on five polymorphisms of four genes with 24 men whose reactions to alcohol had been above the median. Results: The 14 men with the LL genotype of the serotonin transporter (5-HTT) polymorphism and the seven with the Pro/Ser genotype of the GABA(Aα6) polymorphism had demonstrated lower LR scores at about age 20, and had significantly higher proportions of alcoholics than the other genotypes for those loci. All four subjects with combined LL and Pro/Ser genotypes had developed alcoholism and demonstrated the lowest LR scores overall. There was no evidence that two polymorphisms of the 5-HT(2A) receptor gene and one of the 5-HT(2C) receptor gene were related to LR or alcoholism in this sample. Conclusions: These results are consistent with animal and human studies suggesting a possible role for genetic variation in the GABA(Aα6) and the serotonin transporter in the reaction to alcohol and the alcoholism risk.

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