Case Control Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatry. Apr 19, 2025; 15(4): 102182
Published online Apr 19, 2025. doi: 10.5498/wjp.v15.i4.102182
Association and functional study of ATP6V1D and GPHN gene polymorphisms with depression in Chinese population
Peng Liang, Jing-Jie Chen, Xue Yang, Rui Long, Yue Li, Zi-Ling Wang, Ping-Liang Yang, Yun-Dan Liang
Peng Liang, Jing-Jie Chen, Rui Long, Yue Li, Zi-Ling Wang, Yun-Dan Liang, Department of Basic Medicine, Chengdu Medical College, Chengdu 610500, Sichuan Province, China
Xue Yang, Department of Geriatric Psychiatry, The First Psychiatric Hospital of Harbin, Harbin 150001, Heilongjiang Province, China
Ping-Liang Yang, Department of Anesthesiology, The First Affiliated Hospital of Chengdu Medical College, Chengdu 610500, Sichuan Province, China
Co-first authors: Peng Liang and Jing-Jie Chen.
Co-corresponding authors: Ping-Liang Yang and Yun-Dan Liang.
Author contributions: Liang P and Chen JJ performed the experiments, wrote and revise the manuscript, they contributed equally to this article, they are the co-first authors of this manuscript; Yang X, Long R, Li Y, Wang ZL helped with literature reviews, experiments and data analysis; Liang YD and Yang PL designed the study and corrected the manuscript, they contributed equally to this article, they are the co-corresponding authors of this manuscript; and all the authors read and approved the manuscript.
Supported by the Natural Science Foundation of Sichuan, China, No. 2022NSFSC0778; Research Project Foundation of Sichuan Applied Psychology Research Center, No. CSXL-24202; Foundation of Sichuan Clinical Research Center for Geriatrics, No. 24LHLNYX1-04 and No. 24LHLNYX1-06; and the Key Laboratory Foundation for Development and Regeneration of Sichuan Province, No. 24LHFYSZ1-25.
Institutional review board statement: This study was approved by the Medical Ethics Committee of Chengdu medical college, approval No. 201815.
Informed consent statement: All patients gave informed consent.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at liangyundan2004@126.com.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yun-Dan Liang, PhD, Associate Professor, Department of Basic Medicine, Chengdu Medical College, No. 783 Xindu Avenue, Chengdu 610500, Sichuan Province, China. liangyundan2004@126.com
Received: October 11, 2024
Revised: January 20, 2025
Accepted: February 18, 2025
Published online: April 19, 2025
Processing time: 165 Days and 6 Hours
Abstract
BACKGROUND

Depression is a disease with a significant global social burden. Single nucleotide polymorphisms (SNPs) are correlated with the development of depression. This study investigates the relationship between polymorphisms in the GPHN and ATP6V1D gene promoter regions and susceptibility to depression in the Chinese population.

AIM

To provide new insights into identifying SNPs for predicting depression in the Chinese population.

METHODS

We conducted a case-control study involving 555 individuals with depression and 509 healthy controls. GPHN rs8020095 and ATP6V1D rs3759755, rs10144417, rs2031564, and rs8016024 in the promoter region were genotyped using next-generation sequencing. Dual luciferase reporter genes were employed to assess the transcriptional activity of promoter regions for each SNP genotype, with transcription factors binding to each site predicted using the JASPAR database.

RESULTS

Compared to healthy controls, the ATP6V1D promoter rs10144417 AG genotype (P = 0.015), rs3759755 AC/CC genotype (P = 0.036), and GPHN gene rs8020095 GA and AA genotypes (GA: P = 0.028, GG: P = 0.025) were significantly associated with a lower prevalence of depression. Linked disequilibria were present in five SNPs, with the AGATA haplotype frequency in patients significantly lower than in healthy subjects (P = 0.023). Luciferase activity of the rs3759755-A recombinant plasmid was significantly higher than that of the rs3759755-C recombinant plasmid (P = 0.026), and the rs8020095-A recombinant plasmid activity was significantly higher than that of the rs8020095-G recombinant plasmid (P = 0.001). Transcription factors orthodenticle homeobox 2, orthodenticle homeobox 1, forkhead box L1, NK homeobox 3-1, and nuclear factor, interleukin 3 regulated demonstrated binding affinity with rs3759755A > C and rs8020095A > G.

CONCLUSION

This study demonstrates that SNPs (rs3759755 and rs10144417) in the promoter region of the ATP6V1D and SNP (rs8020095) of GPHN are indeed associated with susceptibility to depression.

Keywords: Single nucleotide polymorphism; Genetic susceptibility; Depression; ATP6V1D; GPHN

Core Tip: Single nucleotide polymorphisms in the promoter region of ATP6V1D and GPHN genes are associated with susceptibility to depression in the Chinese population. The genetic variants examined in this study may be linked to protective factors for depression. This study demonstrates that rs3759755, rs10144417 and rs8020095 show significant differences between patients with depression and control subjects in China. These findings offer new insights into identifying single nucleotide polymorphisms that could be used to predict depression in the Chinese population.