Relationship between KCNH2 and CACNA1C gene polymorphisms and cognitive function in patients with schizophrenia

doi:10.3969/j.issn.1673-8640.2023.08.007

Abstract

Abstract:

Objective To investigate the relationship between KCNH2 and CACNA1C gene polymorphisms and cognitive function in patients with schizophrenia. Methods Totally，210 patients with schizophrenia in remission in Anning Hospital from June 2017 to June 2021 were enrolled as study group. Totally，210 healthy volunteers in the same period were enrolled as control group. CACNA1C rs1006737 and KCNH2 rs38007792 gene polymorphisms were determined. The Montreal cognitive assessment（MoCA） was used. The event-related potential（ERP），the latency and amplitude of mismatch negativity（MMN）and P300 were evaluated. MoCA score，MMN，P300 latency and amplitude of patients with different genotypes were compared. Results Compared with control group，instudy group，the distribution frequency of TT genotype at KCNH2 rs3800779 locus was decreased（P<0.05），the distribution frequency of TG genotype was increased（P<0.05），the distribution frequency of T allele was decreased（P<0.05），and the distribution frequency of G allele was increased（P<0.05）. The distribution frequency of AG genotype at CACNA1C rs1006737 locus was increased（P<0.05），GG genotype distribution frequency was decreased（P<0.05），A allele distribution frequency was increased（P<0.05），and G allele distribution frequency was decreased（P<0.05）. Compared with patients with GG genotype at KCNH2 rs3800779 locus，the patients with TT and TG genotypes had decreased MoCA scores（P<0.05），both MMN and P300 latencies were longer（P<0.05），and amplitudes were smaller（P<0.05）. Compared with patients with GG genotype at CACNA1C rs1006737 locus，the patients with AA and AG genotypes had decreased MoCA scores（P<0.05），both MMN and P300 latencies were longer（P<0.05），and amplitudes were smaller（P<0.05）. Conclusions KCNH2 and CACNA1C gene polymorphisms affect the cognitive function of patients with schizophrenia.

Key words: Schizophrenia, Gene polymorphism, Cognitive function

CLC Number:

R446.1

PENG Shouning, DENG Weicong, FU Yanbo, WU Yanni. Relationship between KCNH2 and CACNA1C gene polymorphisms and cognitive function in patients with schizophrenia[J]. Laboratory Medicine, 2023, 38(8): 742-747.

Figures/Tables 3

References 29

[1]	李嘉慧, 刘建鹏, 潘智林, 等. 精神分裂症患者认知功能损伤的神经生物学基础和电生理表现[J]. 中国医学物理学杂志, 2020, 37(1):115-121.
[2]	SHI X J, FAN F C, LIU H, et al. Traditional Chinese medicine decoction combined with antipsychotic for chronic schizophrenia treatment:a systematic review and meta-analysis[J]. Front Pharmacol, 2020, 11:616088. DOI URL
[3]	HOGENAAR J T T, VAN BOKHOVEN H. Schizophrenia:complement cleaning or killing[J]. Genes(Basel), 2021, 12(2):259.
[4]	THILAKAVATHI B, SHENBAGA DEVI S, MALAIAPPAN M, et al. EEG power spectrum analysis for schizophrenia during mental activity[J]. Australas Phys Eng Sci Med, 2019, 42(3):887-897. DOI
[5]	REFISCH A, KOMATSUZAKI S, UNGELENK M, et al. Analysis of CACNA1C and KCNH2 risk variants on cardiac autonomic function in patients with schizophrenia[J]. Genes(Basel), 2022, 13(11):2132.
[6]	CHEN M, JIANG Q, ZHANG L. CACNA1C gene rs1006737 polymorphism affects cognitive performance in chinese han schizophrenia[J]. Neuropsychiatr Dis Treat, 2022, 18:1697-1704. DOI URL
[7]	SCOTTI-MUZZI E, CHILE T, VALLADA H, et al. Association between CACNA1C gene rs100737 polymorphism and glutamatergic neurometabolites in bipolar disorder[J]. Eur Neuropsychopharmacol, 2022, 59:26-35. DOI URL
[8]	ZHU X, LI R, KANG G, et al. CACNA1C polymorphism(rs2283291)is associated with schizophrenia in chinese males:a case-control study[J]. Dis Markers, 2019, 2019:8062397.
[9]	GUARDIOLA-RIPOLL M, ALMODÓVAR-PAYÁ C, LUBEIRO A, et al. New insights of the role of the KCNH2 gene in schizophrenia:an fMRI case-control study[J]. Eur Neuropsychopharmacol, 2022, 60:38-47. DOI URL
[10]	WANG Y, LIU Z, LU J, et al. Biological evaluation and in silico studies of novel compounds as potent TAAR1 agonists that could be used in schizophrenia treatment[J]. Front Pharmacol, 2023, 14:1161964. DOI URL
[11]	LUBEIRO A, FATJÓ-VILAS M, GUARDIOLA M, et al. Analysis of KCNH2 and CACNA1C schizophrenia risk genes on EEG functional network modulation during an auditory odd-ball task[J]. Eur Arch Psychiatry Clin Neurosci, 2022, 270(4):433-442. DOI
[12]	VANWOERDEN S, STEPP S D. The Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition,alternative model conceptualization of borderline personality disorder:a review of the evidence[J]. Personal Disord, 2022, 13(4):402-406. DOI URL
[13]	王献丽, 乌建安, 杜锋. 脑电图和事件相关电位在精神分裂症认知功能评估中的应用[J]. 医学信息, 2019, 32(13):97-99.
[14]	ZHU D, YIN J, LIANG C, et al. CACNA1C(rs1006737)may be a susceptibility gene for schizophrenia:an updated meta-analysis[J]. Brain Behav, 2019, 9(6):e01292. DOI URL
[15]	ZHANG Z, WANG Y, ZHANG Q, et al. The effects of CACNA1C gene polymorphism on prefrontal cortex in both schizophrenia patients and healthy controls[J]. Schizophr Res, 2019, 204:193-200. DOI URL
[16]	GUARDIOLA-RIPOLL M, ALMODÓVAR-PAYÁ C, LUBEIRO A, et al. A functional neuroimaging association study on the interplay between two schizophrenia genome-wide associated genes(CACNA1C and ZNF804A)[J]. Eur Arch Psychiatry Clin Neurosci, 2022, 272(7):1229-1239. DOI
[17]	TANAKA Y, HAYASHI K, FUJINO N, et al. Functional analysis of KCNH2 gene mutations of type 2 long QT syndrome in larval zebrafish using microscopy and electrocardiography[J]. Heart Vessels, 2019, 34(1):159-166. DOI
[18]	陈诚, 王惠玲, 王高华, 等. 抑郁症与精神分裂症患者静息态功能磁共振成像与认知功能的差异[J]. 中华精神科杂志, 2020, 53(5):377-383.
[19]	JANG K I, OH J, JUNG W, et al. Unsuccessful reduction of high-frequency alpha activity during cognitive activation in schizophrenia[J]. Psychiatry Clin Neurosci, 2019, 73(3):132-139. DOI URL
[20]	YÜKSEL M, MURPHY M, RIPPE J, et al. Decreased mismatch negativity and elevated frontal-lateral connectivity in first-episode psychosis[J]. J Psychiatr Res, 2021, 144:37-44. DOI PMID
[21]	LIU Y P, WU X, XIA X, et al. The genome-wide supported CACNA1C gene polymorphisms and the risk of schizophrenia:an updated meta-analysis[J]. BMC Med Genet, 2020, 21(1):159. DOI
[22]	MOON A L, BRYDGES N M, WILKINSON L S, et al. Cacna1c hemizygosity results in aberrant fear conditioning to neutral stimuli[J]. Schizophr Bull, 2020, 46(5):1231-1238. DOI URL
[23]	LUO N, TIAN L, CALHOUN V D, et al. Brain function,structure and genomic data are linked but show different sensitivity to duration of illness and disease stage in schizophrenia[J]. Neuroimage Clin, 2019, 23:101887. DOI URL
[24]	BERDENIS VAN BERLEKOM A, NOTMAN N, SNEEBOER M A, et al. DNA methylation differences in cortical grey and white matter in schizophrenia[J]. Epigenomics, 2021, 13(15):1157-1169. DOI PMID
[25]	ABDOLALIZADEH A, OSTADRAHIMI H, MOHAJER B, et al. White matter microstructural properties associated with impaired attention in chronic schizophrenia:a multi-center study[J]. Psychiatry Res Neuroimaging, 2020, 302:111105. DOI URL
[26]	MIO C, PASSON N, BALDAN F, et al. CACNA1C haploinsufficiency accounts for the common features of interstitial 12p13.33 deletion carriers[J]. Eur J Med Genet, 2020, 63(4):103843. DOI URL
[27]	BAINS S, ZHOU W, DOTZLER S M, et al. Suppression and replacement gene therapy for KCNH2-mediated arrhythmias[J]. Circ Genom Precis Med, 2022, 15(6):e003719.
[28]	REN M, HU Z, CHEN Q, et al. KCNH2-3.1 mediates aberrant complement activation and impaired hippocampal-medial prefrontal circuitry associated with working memory deficits[J]. Mol Psychiatry, 2020, 25(1):206-229. DOI
[29]	HASHIMOTO R, OHI K, YASUDA Y, et al. The KCNH2 gene is associated with neurocognition and the risk of schizophrenia[J]. World J Biol Psychiatry, 2013, 14(2):114-120. DOI URL