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Female-specific effects of the catechol-O-methyl transferase Val¹⁵⁸Met gene polymorphism on working memory-related brain function.

ABSTRACT: The catechol-O-methyltransferase (COMT) Val¹⁵⁸Met polymorphism has been associated with working memory (WM) in many studies, but the results have not been consistent. One plausible explanation is sex-specific effects of this polymorphism as reported in several studies. The current study aimed to explore the sex-specific effects of the COMT Val¹⁵⁸Met polymorphism on WM-related brain function in an elderly sample. We found that Val homozygotes outperformed Met allele carriers on the backward digit span subtest for both males and females. The triangular part of the left inferior frontal gyrus and the left inferior temporal gyrus exhibited higher activation in Met allele carriers compared with Val homozygotes during the n-back task, while the background functional connectivity (bFC) between the left angular gyrus (ANG) and the right ANG was enhanced in Val homozygotes as compared to Met allele carriers. Finally, the associations between brain activation, bFC (among various regions), and WM performance were identified only in specific genotype groups of the female participants. These findings provide new insights into the role of COMT Val¹⁵⁸Met gene polymorphism in brain function, particularly its female-specific nature.

SUBMITTER: Fan J

PROVIDER: S-EPMC7762470 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Female-specific effects of the catechol-O-methyl transferase Val158Met gene polymorphism on working memory-related brain function.

Fan Jialing J Yang Caishui C Liu Zhen Z Li He H Han Yan Y Chen Kewei K Chen Chuansheng C Wang Jun J Zhang Zhanjun Z

Aging 20201122 23

The catechol-O-methyltransferase (COMT) Val158Met polymorphism has been associated with working memory (WM) in many studies, but the results have not been consistent. One plausible explanation is sex-specific effects of this polymorphism as reported in several studies. The current study aimed to explore the sex-specific effects of the COMT Val158Met polymorphism on WM-related brain function in an elderly sample. We found that Val homozygotes outperformed Met a ...[more]

PMID: 33221753

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Project description:IntroductionGreen tea(GT) is able to increase energy expenditure(EE) and fat oxidation(FATox) via inhibition of catechol-O-methyl transferase(COMT) by catechins. However, this does not always appear unanimously because of large inter-individual variability. This may be explained by different alleles of the functional COMT Val108/158Met polymorphism that are associated with COMT enzyme activity; high-activity enzyme, COMT(H)(Val/Val genotype), and low-activity COMT(L)(Met/Met genotype).MethodsFourteen Caucasian subjects (BMI: 22.2±2.3 kg/m2, age: 21.4±2.2 years) of whom 7 with the COMT(H)-genotype and 7 with the COMT(L)-genotype were included in a randomized, cross-over study in which EE and substrate oxidation were measured with a ventilated-hood system after decaffeinated GT and placebo(PL) consumption.ResultsAt baseline, EE, RQ, FATox and carbohydrate oxidation(CHOox) did not differ between groups. Significant interactions were observed between COMT genotypes and treatment for RQ, FATox and CHOox (p<0.05). After GT vs. PL, EE(GT: 62.2 vs. PL: 35.4 kJ.3.5 hrs; p<0.01), RQ(GT: 0.80 vs. PL: 0.83; p<0.01), FATox(GT: 18.3 vs. PL: 15.3 g/d; p<0.001) and CHOox(GT: 18.5 vs. PL: 24.3 g/d; p<0.001) were significantly different for subjects carrying the COMT(H) genotype, but not for subjects carrying the COMT(L) genotype (EE, GT: 60.3 vs. PL: 51.7 kJ.3.5 hrs; NS), (RQ, GT: 0.81 vs. PL: 0.81; NS), (FATox, GT: 17.3 vs. PL: 17.0 g/d; NS), (CHOox, GT: 22.1 vs. PL: 21.4 g/d; NS).ConclusionSubjects carrying the COMT(H) genotype increased energy expenditure and fat-oxidation upon ingestion of green tea catechins vs, placebo, whereas COMT(L) genotype carriers reacted similarly to GT and PL ingestion. The differences in responses were due to the different responses on PL ingestion, but similar responses to GT ingestion, pointing to different mechanisms. The different alleles of the functional COMT Val108/158Met polymorphism appear to play a role in the inter-individual variability for EE and FATox after GT treatment.Trial registrationNederlands Trial register NTR1918.

Dataset Information

Female-specific effects of the catechol-O-methyl transferase Val¹⁵⁸Met gene polymorphism on working memory-related brain function.

Publications

Female-specific effects of the catechol-O-methyl transferase Val<sup>158</sup>Met gene polymorphism on working memory-related brain function.

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