Polymorphisms in Catechol-
            <i>O</i>
            -Methyltransferase Modify Treatment Effects of Aspirin on Risk of Cardiovascular Disease

Hall, Kathryn T.; Nelson, Christopher P.; Davis, Roger B.; Buring, Julie E.; Kirsch, Irving; Mittleman, Murray A.; Loscalzo, Joseph; Samani, Nilesh J.; Ridker, Paul M.; Kaptchuk, Ted J.; Chasman, Daniel I.

doi:10.1161/atvbaha.114.303845

Cited by 39 publications

(56 citation statements)

References 36 publications

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“…Low COMT activity in the cerebral cortex was found in rats with hypertension compared with normal controls (68), suggesting that COMT activity may regulate blood flow in the cortex. In line with this idea, a recent population study shows that subjects with the Met/Met genotype have significantly higher incidences of cardiovascular disease than subjects with the Val/Val genotype (69). In the present study, subjects with the Met/Met genotype who have lower COMT activity may have experienced less blood vessel dilation during immersion compared with the subjects with the Val/Val genotype.…”

Section: Discussionsupporting

confidence: 76%

Brain white matter structure and COMT gene are linked to second-language learning in adults

Mamiya

Richards

Coe

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Adult human brains retain the capacity to undergo tissue reorganization during second-language learning. Brain-imaging studies show a relationship between neuroanatomical properties and learning for adults exposed to a second language. However, the role of genetic factors in this relationship has not been investigated. The goal of the current study was twofold: (i) to characterize the relationship between brain white matter fiber-tract properties and second-language immersion using diffusion tensor imaging, and (ii) to determine whether polymorphisms in the catechol-O-methyltransferase (COMT) gene affect the relationship. We recruited incoming Chinese students enrolled in the University of Washington and scanned their brains one time. We measured the diffusion properties of the white matter fiber tracts and correlated them with the number of days each student had been in the immersion program at the time of the brain scan. We found that higher numbers of days in the English immersion program correlated with higher fractional anisotropy and lower radial diffusivity in the right superior longitudinal fasciculus. We show that fractional anisotropy declined once the subjects finished the immersion program. The relationship between brain white matter fiber-tract properties and immersion varied in subjects with different COMT genotypes. Subjects with the Methionine (Met)/Valine (Val) and Val/Val genotypes showed higher fractional anisotropy and lower radial diffusivity during immersion, which reversed immediately after immersion ended, whereas those with the Met/Met genotype did not show these relationships. Statistical modeling revealed that subjects' grades in the language immersion program were best predicted by fractional anisotropy and COMT genotype.genetic variation | short-term plasticity | dopamine S econd-language learning in adulthood is becoming increasingly prevalent as globalization advances. Previous studies show that gray matter volume and density are related to foreign language speech learning (1, 2), and that the degree of volumetric change in an individual predicts the level of foreign language proficiency achieved by that person (3, 4). Recent studies using diffusion tensor imaging (DTI) techniques further show that diffusion properties of brain white matter structure are correlated with foreign language learning (5-7). One of these studies demonstrated that the changes in diffusion properties predicted students' second-language proficiency at the end of a language immersion program (7). These findings suggest that the properties of brain structure change with the acquisition of a new language, and that the adult human brain is capable of tissue reorganization in response to intense use of a new language after the putative "critical period."What remains unknown is whether and how genetic factors are related to brain white matter fiber-tract properties as learning ensues. Cumulative evidence using DTI analysis has suggested that brain white matter fiber-tract properties are related to skill learning ...

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Section: Discussionsupporting

confidence: 76%

Brain white matter structure and COMT gene are linked to second-language learning in adults

Mamiya

Richards

Coe

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…The rs4680GG genotype has been associated with a high risk of hypertension (33) and CVD (34), whereas the rs4860AA genotype has been shown to be protective against myocardial infarction in hypertensive patients (35). In contrast, the low COMT activity of the rs4860AA genotype has been shown to be an independent risk factor for acute coronary events in Finnish men (36).…”

Section: Figurementioning

confidence: 99%

Protective effect of homovanillyl alcohol on cardiovascular disease and total mortality: virgin olive oil, wine, and catechol-methylathion

Torre

Corella

Castañer

et al. 2017

The American Journal of Clinical Nutrition

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Background: Hydroxytyrosol is a phenolic compound that is present in virgin olive oil (VOO) and wine. Hydroxytyrosol-related foods have been shown to protect against cardiovascular disease (CVD). Objective: We investigated the associations between hydroxytyrosol and its biological metabolite, 3-O-methyl-hydroxytyrosol, also known as homovanillyl alcohol (HVAL), with CVD and total mortality. Design: We included 1851 men and women with a mean 6 SD age of 66.8 6 6 y at high risk of CVD from prospective cohort data. The primary endpoint was a composite of myocardial infarction, stroke, and death from cardiovascular causes; the secondary endpoint was all-cause mortality. Twenty-four-hour urinary hydroxytyrosol and HVAL and catechol-O-methyltransferase (COMT) rs4680 genotypes were measured. Results: After multivariable adjustment, all biomarkers were associated, as a continuous variable, with lower CVD risk, but only HVAL showed a strong inverse association (HR: 0.44; 95% CI: 0.25, 0.80) for the comparison between quintiles. Only HVAL, as a continuous variable, was associated with total mortality (HR: 0.81; 95% CI: 0.70, 0.95). Individuals in the highest quintile of HVAL compared with the lowest had 9.2 (95% CI: 3.5, 20.8) and 6.3 (95% CI: 2.3, 12.1) additional years of life or years free of CVD, respectively, after 65 y. Individuals with the rs4680GG genotype had the highest HVAL concentrations (P = 0.05). There was no association between COMT genotypes and events or interaction between COMT genotypes and HVAL concentrations. Conclusions: We report, for the first time to our knowledge, an independent association between high urinary HVAL concentrations and a lower risk of CVD and total mortality in elderly individuals. VOO and wine consumption and a high metabolic COMT capacity for methylation are key factors for high HVAL concentrations. The association that stems from our results reinforces the benefits of 2 key components of the Mediterranean diet (wine and VOO). This trial was registered at www.predimed.es as ISRCTN35739639.

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“…In this cohort, women were randomly allocated to aspirin or vitamin E, and compared with placebo at 10 years of follow-up. Hall and colleagues have utilized this cohort to examine the effects of the polymorphism (rs4680) of COMT on CVD incidence (17). We considered a subset of the WGHS women allocated to placebo, and used an age-adjusted model (n = 5,814) and a fully adjusted model (n = 5,143) to examine whether the placebome module contains significantly more genes with SNPs that modify the outcome (total CVD and major CVD incidence) in the placebo arm.…”

Section: Resultsmentioning

confidence: 99%

“…Conversely, in other proximal placebome conditions, such as depression (31) and schizophrenia (32), which are known to have high placebo-related responses, activation of the placebome can be presumed to be efficacious in large subsets of patients. Placebome seed genes like COMT have been associated with myriad diseases, including cancer (33), preeclampsia (34), Parkinson disease (35), CVD (17), and psychiatric disorders (36). The proximity of the placebome to diseases that affect women likely derives from the functional interaction of COMT P values were adjusted using the Bonferroni procedure.…”

Section: Resultsmentioning

confidence: 99%

Network analysis of the genomic basis of the placebo effect

Wang¹,

Hall²,

Giulianini³

et al. 2017

JCI Insight

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Polymorphisms in Catechol- O -Methyltransferase Modify Treatment Effects of Aspirin on Risk of Cardiovascular Disease

Cited by 39 publications

References 36 publications

Brain white matter structure and COMT gene are linked to second-language learning in adults

Brain white matter structure and COMT gene are linked to second-language learning in adults

Protective effect of homovanillyl alcohol on cardiovascular disease and total mortality: virgin olive oil, wine, and catechol-methylathion

Network analysis of the genomic basis of the placebo effect

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