Association and functional study of ATP6V1D and GPHN gene polymorphisms with depression in Chinese population  

作　　者：Peng Liang Jing-Jie Chen Xue Yang Rui Long Yue Li Zi-Ling Wang Ping-Liang Yang Yun-Dan Liang 

机构地区：[1]Department of Basic Medicine,Chengdu Medical College,Chengdu 610500,Sichuan Province,China [2]Department of Geriatric Psychiatry,The First Psychiatric Hospital of Harbin,Harbin 150001,Heilongjiang Province,China [3]Department of Anesthesiology,The First Affiliated Hospital of Chengdu Medical College,Chengdu 610500,Sichuan Province,China

出　　处：《World Journal of Psychiatry》2025年第4期73-85,共13页世界精神病学杂志(英文)

基　　金：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.

摘　　要：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 nextgeneration 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 werepresent 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 thers3759755-C recombinant plasmid (P = 0.026), and the rs8020095-A recombinant plasmid activity was significantlyhigher than that of the rs8020095-G recombinant plasmid (P = 0.001). Transcription factors orthodenticle homeobox2, orthodenticle homeobox 1, forkhead box L1, NK homeobox 3-1, and nuclear factor, interleukin 3 regulateddemonstrated binding affinity with rs3759755A > C and rs8020095A > G.CONCLUSIONThis 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.

关 键 词：Single nucleotide polymorphism Genetic susceptibility DEPRESSION ATP6V1D GPHN 

分 类 号：R74[医药卫生—神经病学与精神病学]