High and low activity alleles of catechol-O-methyltransferase gene: ethnic difference and possible association with Parkinson's disease

Nanko, Shinichiro; Ueki, Akira; Otsuka, Emiko; Hattori, Mineko; Hoda, Farzana; Vallada, Homero; Arranz, Maria; Collier, David

doi:10.1016/s0304-3940(96)13289-4

Cited by 111 publications

(76 citation statements)

References 15 publications

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“…There is a strong trend towards deviation from Hardy-Weinberg equilibrium in the male completers (w 2 ¼ 3.6; df ¼ 1, p ¼ 0.057), while the genotype distributions in male/female controls and female suicide completers are in Hardy-Weinberg equilibrium. The allele frequencies in the controls were similar to those previously established for a Japanese population (Kunugi et al, 1997a;Ohmori et al, 1998;Ohara et al, 1998).…”

Section: Statistical Analysessupporting

confidence: 84%

Association between Catechol-O-Methyltransferase Functional Polymorphism and Male Suicide Completers

Ono

Sato

Nushida

et al. 2004

Neuropsychopharmacol

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Suicide has been suggested to involve catecholaminergic dysfunction and to be related to genetics. Catechol-O-methyltransferase (COMT) 158Val/Met polymorphism (GenBank Accession No. Z26491) is a polymorphism of the gene encoding COMT, a major enzyme in catecholamine inactivation. The COMT 158Val/Met polymorphism affects COMT activity, that is, the alleles encoding Val and Met are associated with relatively high and relatively low COMT activity, respectively. In this study, we hypothesized that the COMT 158Val/Met polymorphism is associated with suicide. The study population consisted of 163 suicide completers (112 males and 51 females). We found that the genotype distribution of the COMT 158Val/Met polymorphism was significantly different between male suicide completers and male controls (p ¼ 0.036), while the frequency of the Val/Val genotype, a highactivity COMT genotype, was significantly less in male suicide completers than in male controls (OR: 0.52; 95% CL: 0.31-0.89; p ¼ 0.016). However, this was not the case in females. Our results suggest that the Val/Val genotype is a protective factor against suicide in males.

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Section: Statistical Analysessupporting

confidence: 84%

Association between Catechol-O-Methyltransferase Functional Polymorphism and Male Suicide Completers

Ono

Sato

Nushida

et al. 2004

Neuropsychopharmacol

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“…Also, differences in race distribution could influence the findings, as it is known that allele frequencies, as well as linkage disequilibria, may vary among races. For example, Asians and African-Americans have a lower frequency of the low activity allele of the COMT Val158Met gene polymorphism than Caucasians [68].…”

Section: Discussionmentioning

confidence: 99%

Pharmacogenetics of Antiparkinsonian Drug Treatment: A Systematic Review

et al. 2007

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Pharmacotherapy is the mainstay in the treatment of Parkinson’s disease and the armamentarium of drugs available for the therapy of this disease is still expanding. Anti-Parkinson’s disease drugs are effective in reducing the physical symptoms, such as hypokinesia, bradykinesia, rigidity and tremor. However, there is a large interindividual variability in response to anti-Parkinson’s disease drugs with respect to both drug efficacy and toxicity. It is thought that genetic variability in genes encoding drug-metabolizing enzymes, drug receptors and proteins involved in pathway signaling is an important factor in determining interindividual variability in drug response. Pharmacogenetics aims at identifying genetic markers associated with drug response. Ideally, knowledge of these genetic markers will enable us to predict an individual’s drug response in terms of both efficacy and toxicity. The role of pharmacogenetics in the treatment of Parkinson’s disease is relatively unexplored. Therefore, we aim to present a systematic review of the published pharmacogenetic studies in Parkinson’s disease and to describe polymorphic genes of interest for future research.

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“…Two forms of human COMT have been identified, a cytoplasmic soluble form (S-COMT) and a membrane-bound form (MB-COMT) located in the cytosolic side of the rough endoplasmic reticulum The S-COMT is predominantly expressed in the human liver, intestine and kidney (Taskinen et al, 2003), whereas the membrane-bound form is more highly expressed in all regions of the human central nervous system (Tunbridge et al, 2006). A common functional polymorphism at codons 108 and 158 in the genes coding for S-COMT and MB-COMT (COMT Val 108/158 Met), respectively, has been examined in relationship to a number of neurological disorders involving the noradrenergic or dopaminergic systems, such as schizophrenia (Park et al, 2002) or Parkinson's disease (Kunugi et al, 1997). It has also been suggested that a common functional genetic polymorphism in the COMT gene may contribute to the etiology of alcoholism (Wang et al, 2001).…”

Section: O-methylationmentioning

confidence: 99%