Thermal stability and the biochemical genetics of erythrocyte catechol‐O‐methyltransferase and plasma dopamine‐β‐hydroxylase

Weinshilboum, Richard M.; Dunnette, Joel

doi:10.1111/j.1399-0004.1981.tb00740.x

Cited by 45 publications

(19 citation statements)

References 40 publications

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“…methionine). This polymorphism has been shown to substantially aVect COMT enzyme activity, such that homozygosity for the valine allele shows 3-4 times greater activity than homozygosity for the methionine allele (Lotta et al 1995;Scanlon et al 1979;Weinshilboum and Dunnette 1981). Despite the potential relevance of this functional polymorphism to ADHD and an initial small study suggesting that the valine allele of this polymorphism was associated with increased risk for ADHD (Eisenberg et al 1999), the majority of studies have reported negative results (Barr et al 1999;Hawi et al 2000b;Payton et al 2001).…”

Section: Catechol-o-methyl-transferase (Comt)mentioning

confidence: 88%

Candidate gene studies of ADHD: a meta-analytic review

2009

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Quantitative genetic studies (i.e., twin and adoption studies) suggest that genetic influences contribute substantially to the development of attention deficit hyperactivity disorder (ADHD). Over the past 15 years, considerable efforts have been made to identify genes involved in the etiology of this disorder resulting in a large and often conflicting literature of candidate gene associations for ADHD. The first aim of the present study was to conduct a comprehensive meta-analytic review of this literature to determine which candidate genes show consistent evidence of association with childhood ADHD across studies. The second aim was to test for heterogeneity across studies in the effect sizes for each candidate gene as its presence might suggest moderating variables that could explain inconsistent results. Significant associations were identified for several candidate genes including DAT1, DRD4, DRD5, 5HTT, HTR1B, and SNAP25. Further, significant heterogeneity was observed for the associations between ADHD and DAT1, DRD4, DRD5, DBH, ADRA2A, 5HTT, TPH2, MAOA, and SNAP25, suggesting that future studies should explore potential moderators of these associations (e.g., ADHD subtype diagnoses, gender, exposure to environmental risk factors). We conclude with a discussion of these findings in relation to emerging themes relevant to future studies of the genetics of ADHD.

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Section: Catechol-o-methyl-transferase (Comt)mentioning

confidence: 88%

Candidate gene studies of ADHD: a meta-analytic review

2009

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“…COMT enzyme activity is genetically polymorphic with a trimodal distribution: high activity for the Val/Val genotype, intermediate activity for the Val/Met genotype, and low activity for the Met/Met genotype. The Met/Met genotype has a 3-to 4-fold lower enzyme activity than the Val/Val genotype [13,16] . This single nucleotide polymorphism is widely referred to as the 158Val/Met polymorphism [17] .…”

Section: Introductionmentioning

confidence: 99%

“…COMT is encoded by a single gene localized on chromosome 22q11.1eq11.2. COMT activity is influenced by a common polymorphism, G158A, which causes substantial variations in enzymatic activity [13] . This polymorphism results in a valine (Val) to methionine (Met) substitution at codon 158 of the membrane-bound form of COMT, which corresponds to codon 108 of the soluble form of COMT [14,15] .…”

Section: Introductionmentioning

confidence: 99%

Gender Effect of Catechol-<i>O</i>-Methyltransferase Val158Met Polymorphism on Suicidal Behavior

Lee¹,

Kim²

2011

Neuropsychobiology

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Genetic factors and catecholaminergic dysfunction have been suggested as the etiology of suicide. The catechol-O-methyltransferase (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. We aimed to identify the role of the COMT Val158Met polymorphism in suicidal attempt behavior. The COMT 158Val/Met polymorphisms were analyzed in 197 suicide attempters (male/female: 70/127), 170 control subjects (male/female: 85/85). All subjects were ethnic Korean. The Lethality Suicide Attempt Rating Scale (LSARS) and risk-rescue rating (RRR) system were explored. For the male subjects, there was a significant difference in genotype distributions and allele frequencies between control subjects and suicide attempters. That is, Val/Val genotype and Val carriers were more frequent in suicide attempters than in control subjects. For the female subjects, however, no significant difference was shown in genotype distributions and allele frequencies between control subjects and suicide attempters. There were no significant differences in LSARS and RRR according to the genotypes. The distribution of the COMT 158Val/Met polymorphism showed a biologically meaningful difference between control subjects and suicide attempters among the male subjects although selection bias should be considered.

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“…Grossman et al (1992) and Goodman et al (2002) later found that the Val108 and Met108 variations of the human COMT correlated with the phenotypes of high and low levels of COMT catalytic activity, respectively. However, a more detailed analysis of the catalytic activity of these two forms of COMT revealed a similar catalytic property, although the Met108 variant was more thermolabile (37°C), which could be stabilized by AdoMet binding (Weinshilboum and Dunnette, 1981). Studies have also shown that there was a significant correlation between the COMT heated/control ratios and the levels of enzyme activity in the lysates prepared from hepatic tissue and red blood cells.…”

Section: Discussionmentioning

confidence: 92%

“…Human cytosolic COMT is a polymorphic enzyme. Earlier studies with human liver and red blood cells have shown that the low-activity form of the COMT is slightly more sensitive to heat inactivation than its high-activity form (Scanlon et al, 1979;Weinshilboum and Dunnette, 1981). Using eight representative human placenta samples, we determined in the present study their sensitivity to inhibition by gradually increasing the preincubation temperatures from 30 to 50°C (Fig.…”

Section: Zhu Et Almentioning

confidence: 99%

O-Methylation of Catechol Estrogens by Human Placental Catechol-O-Methyltransferase: Interindividual Differences in Sensitivity to Heat Inactivation and to Inhibition by Dietary Polyphenols

Zhu

Wu²,

Wang³

et al. 2010

Drug Metab Dispos

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ABSTRACT:The human catechol-O-methyltransferase (COMT) is a polymorphic enzyme that catalyzes the O-methylation of catechol estrogens. Recent animal studies showed that placental COMT is involved in the development of placentas and embryos, probably via the formation of 2-methoxyestradiol. In this study, we analyzed a total of 36 human term placentas to determine their cytosolic COMT activity for the O-methylation of catechol estrogens as well as their sensitivity to inhibition by heat and dietary compounds. Large variations (up to 4-fold) in the COMT activity for the formation of methoxyestrogens were noted with different human placental samples. The cytosolic COMTs in different human placentas also displayed considerable differences in their sensitivity to heat inactivation. This differential sensitivity was not associated with the overall catalytic activity for the O-methylation of catechol estrogen substrates. It was observed that there was a positive correlation (r ‫؍‬ 0.760) between the sensitivity of the human placental COMT to heat inactivation and its sensitivity to inhibition by (؊)-epigallocatechin-3-gallate (a well known tea polyphenol with COMT-inhibiting activity) but an inverse correlation (r ‫؍‬ 0.544) between heat inactivation and inhibition by quercetin (another dietary COMT inhibitor). The differences in inhibition by these two dietary compounds are due to different mechanisms of COMT inhibition involved.

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Thermal stability and the biochemical genetics of erythrocyte catechol‐O‐methyltransferase and plasma dopamine‐β‐hydroxylase

Cited by 45 publications

References 40 publications

Candidate gene studies of ADHD: a meta-analytic review

Candidate gene studies of ADHD: a meta-analytic review

Gender Effect of Catechol-<i>O</i>-Methyltransferase Val158Met Polymorphism on Suicidal Behavior

O-Methylation of Catechol Estrogens by Human Placental Catechol-O-Methyltransferase: Interindividual Differences in Sensitivity to Heat Inactivation and to Inhibition by Dietary Polyphenols

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