Browsing by Subject "COMT"

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    Influence of COMT genotype polymorphism on plasma and urine green tea catechin levels in postmenopausal women
    (2014-09) Perry, Alyssa Heather
    Catechins are the major polyphenolic compound in green tea that have been investigated extensively over the past few decades in relation to the treatment of various chronic diseases including diabetes, cardiovascular disease, and cancer. O-methylation is a major Phase II metabolic pathway of green tea catechins (GTCs) via the enzyme catechol-O-methyltransferase (COMT). A single nucleotide polymorphism in the gene coding for COMT leads to individuals with a high-, intermediate-, or low-activity COMT enzyme. An epidemiological case-control study suggests that green tea consumption is associated with reduced risk of breast cancer in women with an intermediate- or low-activity COMT genotype. A cross-sectional analysis discovered that men homozygous for the low-activity COMT genotype showed a reduction in total tea polyphenols in spot urine samples compared to the intermediate- and high-activity genotypes. Several human intervention trials have assessed green tea intake, metabolism, and COMT genotype with conflicting results. The aim of the present study was to determine if the COMT polymorphism would modify the excretion and plasma levels of GTCs in 180 postmenopausal women at high risk for breast cancer consuming a green tea extract supplement containing 1222 mg total catechins daily for 12 months. All participants in the study were a sub-set from the larger parent study "Green Tea and Reduction of Breast Cancer Risk." Thirty subjects with the high-activity COMT genotype, thirty with intermediate-activity COMT genotype, and thirty with low-activity COMT genotype from each of the placebo and treatment groups were analyzed. No statistically significant differences were found in any urinary or plasma catechin metabolite measurements between the homozygous high-activity and homozygous low-activity COMT genotype in the treatment group. Additionally, no differences were found when high-, intermediate-, and low-activity COMT genotypes were all compared in the treatment group. This suggests that the COMT genotype does not play a major role in GTC metabolism. Dosing of GTC and timing of biological samples are important factors that may need further research in future trials evaluating the effect of COMT genotype and GTC metabolism.
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    Working memory subprocesses and catechol-O-methyltransferase Val158Met polymorphism in schizophrenia patients, bipolar disorder patients, and their relatives.
    (2010-07) Dionisio, Daphne
    The present study had several objectives. It sought to determine if deficits in working memory subprocesses of maintenance, monitoring, and manipulation are specific to schizophrenia or are also present in patients with bipolar disorder. It was of interest to additionally determine if working memory deficits are present in the relatives of schizophrenia patients and relatives of bipolar disorder patients. Finally, the association between the COMT Val158Met polymorphism and working memory ability in schizophrenia patients, bipolar disorder patients, and the relatives of these patient groups was investigated. Genotyping data and performance scores for the Spatial Delayed Response Task (i.e. maintenance), Self Ordered Pointing (i.e. monitoring), Digit Span Backwards (i.e. low demand manipulation) and Letter Number Sequencing (i.e. high demand manipulation) were collected for schizophrenia patients, bipolar disorder patients, relatives of schizophrenia patients, relatives of bipolar disorder patients, and nonpsychiatric controls. Results showed worse performance on the maintenance, low demand manipulation, and high demand manipulation working memory subprocesses for schizophrenia patients compared to nonpsychiatric controls and bipolar disorder patients. The relatives of schizophrenia patients also demonstrated impairment in low demand manipulation and high demand manipulation, as well as a trend for worse maintenance performance compared to nonpsychiatric controls. Although no genotype group differences were revealed when examined in a sample combining all diagnostic groups, a few genotype group differences were detected when examined within a sample of schizophrenia patients. These results will be discussed. The results suggest that schizophrenia and bipolar disorder have distinct pathophysiologies, manipulation is promising as an endophenotype for schizophrenia-relevant disease genes, and there may be Val158Met genotype group differences in working memory within schizophrenia patients.