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ORIGINAL RESEARCH article

Front. Psychiatry
Sec. Molecular Psychiatry
Volume 15 - 2024 | doi: 10.3389/fpsyt.2024.1377403

Epigenetic Associations of GPNMB rs199347 Variant with Alcohol Consumption in Parkinson's Disease

Provisionally accepted
Yen-chung Chen Yen-chung Chen 1,2Yi-Chia Liaw Yi-Chia Liaw 3Oswald Ndi Nfor Oswald Ndi Nfor 2Chih-Hsuan Hsiao Chih-Hsuan Hsiao 2Ji-Han Zhong Ji-Han Zhong 2Shey-Lin Wu Shey-Lin Wu 1,4*Yung-Po Liaw Yung-Po Liaw 2*
  • 1 Changhua Christian Hospital, Changhua, Taiwan
  • 2 Chung Shan Medical University, Taichung, Taichung County, Taiwan
  • 3 Taipei Veterans General Hospital, Taipei, Taipei County, Taiwan
  • 4 National Changhua University of Education, Changhua City, Taiwan

The final, formatted version of the article will be published soon.

    Introduction: Alcohol consumption can induce a neuroinflammatory response and contribute to the progression of neurodegeneration. However, its association with Parkinson's disease (PD), the second most common neurodegenerative disorder, remains undetermined. Recent studies suggest that the glycoprotein non-metastatic melanoma protein B (GPNMB) is a potential biomarker for PD. We evaluated the association of rs199347, a variant of the GPNMB gene, with alcohol consumption and methylation upstream of GPNMB.Methods: We retrieved genetic and DNA methylation data obtained from participants enrolled in the Taiwan Biobank (TWB) between 2008 and 2016. After excluding individuals with incomplete or missing information about potential PD risk factors, we included 1,357 participants in our final analyses. We used multiple linear regression to assess the association of GPNMB rs199347 and chronic alcohol consumption (and other potential risk factors) with GPNMB cg17274742 methylation.Results: There was no difference between the distribution of GPNMB rs199347 genotypes between chronic alcohol consumers and the other study participants. A significant interaction was observed between the GPNMB rs199347 variant and alcohol consumption (P =0.0102) concerning cg17274742 methylation. Compared to non-chronic alcohol consumers with the AA genotype, alcohol drinkers with the rs199347 GG genotype had significantly lower levels (hypomethylation) of cg17274742 (P = 0.0187).Conclusion: Alcohol consumption among individuals with the rs199347 GG genotype was associated with lower levels of cg17274742 methylation, which could increase expression of the GPNMB gene, an important neuroinflammatory-related risk gene for PD.

    Keywords: Parkinson Disease, DNA Methylation, Epigenesis, Genetic, Alcohol-Related Disorders, GPNMB

    Received: 29 Jan 2024; Accepted: 27 Jun 2024.

    Copyright: © 2024 Chen, Liaw, Nfor, Hsiao, Zhong, Wu and Liaw. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Shey-Lin Wu, Changhua Christian Hospital, Changhua, Taiwan
    Yung-Po Liaw, Chung Shan Medical University, Taichung, 40201, Taichung County, Taiwan

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