Confirmation of an excess of the high enzyme activity COMT val allele in heroin addicts in a family-based haplotype relative risk study

Ronit Horowitz, Moshe Kotler, Emi Shufman, Shahar Aharoni, Ilana Kremer, Hagit Cohen, Richard P. Ebstein

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

A previous case control study by Vandenbergh et al. [1997: Am J Med Genet 74:439-442] showed an association between the high activity catechol O-methyltransferase (COMT) polymorphism and polysubstance abuse in a group of North American subjects. In the current study we confirm these results by genotyping 38 Israeli heroin addicts and both parents using a robust family-based haplotype relative risk (HRR) strategy. There is an excess of the val COMT allele (likelihood ratio = 4.48, P = 0.03) and a trend for an excess of the val/val COMT genotype (likelihood ratio = 4.97, P = 0.08, 2 df) in the heroin addicts compared to the HRR control group. We also genotyped an additional 101 nonrelated heroin addicts and 126 control subjects using a case control design and found no significant difference in COMT val allele frequency (25.4% vs. 29.7%, likelihood ratio = 1.04, P = 0.31). A significant difference is observed in COMT allele frequency among the three principal Israeli ethnic groups (Ashkenazi Jewish, non-Ashkenazi Jewish, and Palestinian Arab) in a large group of control subjects we have so far examined (chi-square = 7.9, P = 0.019, df = 2, n = 1,422 alleles) suggesting that population stratification is responsible for our failure to observe an excess of the COMT val allele when using the case-control design. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)599-603
Number of pages5
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume96
Issue number5
DOIs
StatePublished - 9 Oct 2000
Externally publishedYes

Keywords

  • Allele frequency
  • Catechol O-methyltransferase
  • Haplotype relative risk
  • Heroin
  • Polymorphism
  • Substance abuse

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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