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Research Paper|Volume 12, Issue 23|pp 23900—23916

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

Jialing Fan1,7, Caishui Yang1,7, Zhen Liu2, He Li3,7, Yan Han4, Kewei Chen5,7, Chuansheng Chen6, Jun Wang1,7, Zhanjun Zhang1,7
  • 1State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, China
  • 2National Institute on Drug Dependence, Peking University, Beijing 100191, China
  • 3Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China
  • 4Department of Neurology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
  • 5Banner Alzheimer’s Institute, Phoenix, AZ 85006, USA
  • 6Department of Psychological Science, University of California, Irvine, CA 92697, USA
  • 7BABRI Centre, Beijing Normal University, Beijing 100875, China
* Equal contributions
Received: June 24, 2020Accepted: August 25, 2020Published: November 22, 2020
https://doi.org/10.18632/aging.104059

Copyright: © 2020 Fan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.