Investigation of genetic risk factors associated with alcoholism

Shoji Harada, Takehito Okubo, Mikihiro Tsutsumi, Shujiro Takase, Taro Muramatsu

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Alcoholism is a multifactorial disease influenced by genetic- environmental interaction. Genetic variation of the receptor may be associated with alcohol dependence due to its modified function in behavioral and physiological responses. In the present study, polymorphic alleles of cholecystokinin B receptor (CCKBR), serotonin 1 A receptor (HT1AR) genes, and mitochondrial DNA were analyzed. DNAs were isolated from the blood samples of 112 healthy controls and 106 alcoholics. Genetic variation was detected by SSCP analysis, followed by direct sequencing of polymerase chain reaction product as well as restriction fragment-length polymorphism. Three different mutations were found in the exon 3 sequence of CCKBR: His (CAT) at aa207 → His (CAC) (5.4%), Arg (CGC) at aa215 → His (CAC) (4.5%), and Val (GTG) at aa138 → Met (ATG) (0.9%) in controls. Genotypic distribution of alcoholics was not significantly different with that in controls. A proline (CCG) to leucine (CTG) substitution at amino acid 16 of HT1AR was found in alcoholics (4.5%) and in controls (4.7%). This mutation site of HT1AR was different in comparison with the variants reported by Nakhai et al. (Biochem Biophys. Res. Commun. 210:530-536, 1995). Analysis of the mitochondrial DNA showed that a 491 bp deletion in the sequence of ATPase exists as heteroplasmy in 58% of alcoholics, but not in controls. Heteroplasmic deletion of mitochondrial DNA may be a useful marker for alcohol abuse. Further study is undergoing to elucidate the cause and significance of this deletion in alcoholics.

Original languageEnglish
JournalAlcoholism: Clinical and Experimental Research
Volume20
Issue number9 SUPPL.
DOIs
Publication statusPublished - 1996
Externally publishedYes

Fingerprint

Alcoholics
Alcoholism
Mitochondrial DNA
Cholecystokinin B Receptor
Alcohols
Single-Stranded Conformational Polymorphism
Mutation
Inborn Genetic Diseases
Sequence Deletion
Polymerase chain reaction
Amino Acid Substitution
Polymorphism
Reaction products
Proline
Leucine
Restriction Fragment Length Polymorphisms
Adenosine Triphosphatases
Exons
Serotonin
Blood

Keywords

  • Alcoholism
  • Cholecystokinin B Receptor
  • Mitochondrial DNA
  • Polymorphism
  • Serotonin 1A Receptor

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

Cite this

Investigation of genetic risk factors associated with alcoholism. / Harada, Shoji; Okubo, Takehito; Tsutsumi, Mikihiro; Takase, Shujiro; Muramatsu, Taro.

In: Alcoholism: Clinical and Experimental Research, Vol. 20, No. 9 SUPPL., 1996.

Research output: Contribution to journalArticle

Harada, Shoji ; Okubo, Takehito ; Tsutsumi, Mikihiro ; Takase, Shujiro ; Muramatsu, Taro. / Investigation of genetic risk factors associated with alcoholism. In: Alcoholism: Clinical and Experimental Research. 1996 ; Vol. 20, No. 9 SUPPL.
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