Epigenetic associations of GPNMB rs199347 variant with alcohol consumption in Parkinson's disease

Yen-Chung Chen; Yi-Chia Liaw; Oswald Ndi Nfor; Chih-Hsuan Hsiao; Ji-Han Zhong; Shey-Lin Wu; Yung-Po Liaw

doi:10.3389/fpsyt.2024.1377403

Epigenetic associations of GPNMB rs199347 variant with alcohol consumption in Parkinson's disease

Front Psychiatry. 2024 Jul 18:15:1377403. doi: 10.3389/fpsyt.2024.1377403. eCollection 2024.

Authors

Yen-Chung Chen^{1

2}, Yi-Chia Liaw³, Oswald Ndi Nfor¹, Chih-Hsuan Hsiao¹, Ji-Han Zhong¹, Shey-Lin Wu^{2

4}, Yung-Po Liaw^{1

5

6}

Affiliations

¹ Department of Public Health and Institute of Public Health, Chung Shan Medical University, Taichung, Taiwan.
² Department of Neurology, Changhua Christian Hospital, Changhua, Taiwan.
³ Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.
⁴ Department of Electrical Engineering, National Changhua University of Education, Changhua, Taiwan.
⁵ Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan.
⁶ Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.

Abstract

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: DNA methylation; GPNMB; Parkinson disease; alcohol-related disorders; epigenesis; genetic.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was funded by the Ministry of Science and Technology (MOST 109–2121-M-040–002; 109–2811-M-040–500; 110–2811-M-040–001; 110- 2121-M-040–002; 111–2811-M-040–001; 111–2121-M-040–002; 111–2811-M- 040–001).