<italic style="font-style: italic">BMAL</italic>1基因单核苷酸多态性与双相情感障碍的关联性研究

闵文蛟; 孙学礼; 邹志礼; 张旭; 陈樾馨; 周波

doi:10.16016/j.2097-0927.202203131

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BMAL1基因单核苷酸多态性与双相情感障碍的关联性研究

神经科学 | 更新时间：2026-02-13

- BMAL1基因单核苷酸多态性与双相情感障碍的关联性研究
- Association between single nucleotide polymorphism of BMAL1 and bipolar disorder
- 陆军军医大学学报 2022年44卷第22期页码：2246-2255
- 作者机构：
  
  1.610072 成都，四川省医学科学院 · 四川省人民医院心身医学中心，四川省精神医学中心
  2.610041 成都，四川大学华西医院心理卫生中心
- 作者简介：
  
  [周波，E-mail：71761715@qq.com ZHOU Bo, E-mail: 71761715@qq.com
- 基金信息：
  
  四川省医学科学院·四川省人民医院青年科学基金(2017QN13);四川省科技厅青年科学基金(2022NSFSC1550);中国医学科学院中央级公益科研基地平台建设项目(2018PT31049);中国医学科学院中央级公益科研基地平台建设项目(2019PT310020);利益冲突声明本文所有作者声明不存在利益冲突
- DOI：10.16016/j.2097-0927.202203131
  中图分类号： R195.4;R394.5;R749.4
- 收稿：2022-03-15，
  
  修回：2022-04-21，
  
  纸质出版：2022-11-30
- 稿件说明：
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闵文蛟, 孙学礼, 邹志礼, 等. BMAL1基因单核苷酸多态性与双相情感障碍的关联性研究[J]. 陆军军医大学学报, 2022,44(22):2246-2255.

Wenjiao MIN, Xueli SUN, Zhili ZOU, et al. Association between single nucleotide polymorphism of BMAL1 and bipolar disorder[J]. Journal of Army Medical University, 2022, 44(22): 2246-2255.
闵文蛟, 孙学礼, 邹志礼, 等. BMAL1基因单核苷酸多态性与双相情感障碍的关联性研究[J]. 陆军军医大学学报, 2022,44(22):2246-2255. DOI： 10.16016/j.2097-0927.202203131.

Wenjiao MIN, Xueli SUN, Zhili ZOU, et al. Association between single nucleotide polymorphism of BMAL1 and bipolar disorder[J]. Journal of Army Medical University, 2022, 44(22): 2246-2255. DOI： 10.16016/j.2097-0927.202203131.

摘要

目的

探讨节律基因

BMAL

1单核苷酸多态性(single nucleotide polymorphism

SNP) 与双相情感障碍(bipolar disorder，BD)易感性及临床特征的关联性。

方法

采用病例对照研究，选取2018年12月至2020年1月在四川大学华西医院心理卫生中心及四川省人民医院心身医学中心门诊及住院就诊的BD患者136例和正常对照者130例，分为BD组与对照组。采用SNapShot分型技术进行外周血

BMAL

1基因的16个SNP位点基因分型，TT3、TT4、FT3、FT4和COR使用电化学发光定量分析进行

检测，促甲状腺激素(thyroid stimulating hormone

TSH)使用ELISA法进行检测，促肾上腺皮质激素(adrenocor ticotropic hormone，ACTH)采用放射免疫分析法进行检测。统计分析节律基因

BMAL

1单核苷酸多态性与双相情感障碍易感性及临床特征的关联性。

结果

BMAL

1基因的rs11022765 C、rs10832022 A和rs6486116 C等位基因携带者在BD组的分布频率均显著高于对照组(

=0.009，0.005，0.010)。rs6486116-rs10832020的CT单倍型在BD组(57.4%) 分布显著高于对照组(48.5%) (

=0.040)；rs10832022-rs11022765-rs11022762的GAT单倍型在BD组(30.1%) 分布显著低于对照组(42.7%) (

=0.003)。rs11022765不同基因型患者的NEO-FFI外倾性因子评分有显著差异(

0.001)。rs10832022、rs11022765不同基因型患者的HPT轴异常率均有显著差异(

=0.013，P=0.012)。

结论

节律基因

BMAL

1的SNP变异可能与BD易感性有关，且与BD特定临床表型相关联。

Abstract

Objective

To identify the association between single nucleotide polymorphism of rhythm gene

BMAL

1 and bipolar disorder (BD) of clinical characteristics and susceptibility.

Methods

The case-control study was conducted on 136 outpatients and inpatients with BD(the BD group) and 130 normal controls (the control group) enrolled in the Mental Health Center of West China Hospital of Sichuan University and Psychosomatic Medicine Center of Sichuan Provincial People's Hospital from December 2018 to January 2020. Sixteen single nucleotide polymorphisms (SNPs) of

BMAL

1 gene were genotyped by SNapShot typing. The levels of TT3

TT4

FT3

FT4 and COR were assayed by electrochemiluminescence immunoassay. Thyroid stimulating hormone (TSH) was measured using ELISA and adrenocor ticotropic hormone (ACTH) was tested by radioimmunoassay. The association between SNPs of

BMAL

1 and BD of susceptibility and clinical characteristics was statistically analyzed.

Results

As for the distribution frequencies

allele carriers of rs1022765-C

rs10832022-A and rs6486116-C were significantly

higher in BD group than those in control group (

=0.009

0.005

0.010). The haplotype analysis showed that the distribution frequency of rs6486116-rs10832020 C-T haplotype in BD group (57.4%) was significantly higher than that in control group (48.5%) (

=0.040); the distribution frequency of rs10832022-rs11022765-rs11022762 G-A-T haplotype was significantly lower in BD group (30.1%) than that in control group (42.7%) (

=0.003). Through multiple logistic regression

the extroversion factor scores of NEO-FFI among patients with different genotypes of rs11022765 were significantly different (

0.001). Meanwhile

the incidences of the abnormal HPT axis among patients with different genotypes of both rs10832022 and rs11022765 were also significantly different (

= 0.013

=0.012).

Conclusion

SNPs of

BMAL

1 is associated with the susceptibility of BD

and also associated with clinical phenotypes.

关键词

Keywords

references

HUANG Y Q, WANG Y, WANG H, et al . Prevalence of mental disorders in China: a cross-sectional epidemiological study[J ] . LancetPsychiatry, 2019, 6(3): 211-224. DOI: 10.1016/S2215-0366(18)30511-X.

LEBOYER M, KUPFER D J. Bipolar disorder: new perspectives in health care and prevention[J]. J Clin Psychiatry, 2010, 71(12): 1689-1695. DOI: 10.4088/JCP.10m06347yel.

SIGITOVA E, FIŠAR Z, HROUDOVÁ J, et al . Biological hypotheses and biomarkers of bipolar disorder[J ] . Psychiatry Clin Neurosci, 2017, 71(2): 77-103. DOI: 10.1111/pcn.12476.

刘幔利, 孟雅婧, 魏巍, 等. 生物节律相关脑功能连接异常与双相情感障碍的相关性[J]. 南方医科大学学报, 2020, 40(6): 822-827. DOI: 10.12122/j.issn.1673-4254.2020.06.08.

LIU M L, MENG Y J, WEI W, et al . Relationship between circadian rhythm related brain dysfunction and bipolar disorder[J ] . J South Med Univ, 2020, 40 (6): 822-827. DOI: 10.12122/j.issn.1673-4254.2020.06.08.

程宇航, 谢静, 何山, 等. 双相障碍患者HPA轴改变与血清蛋白表达谱差异研究[J]. 精神医学杂志, 2015, 28(6): 401-405. DOI: 10.3969/j.issn.2095-9346.2015.06.001.

CHENG Y H, XIE J, HE S, et al . A study of the differences between serum protein expression profile and hypothalamus-pituitary-adrenal (HPA) axis in patients with bipolar disorder[J ] . J Psychiatry, 2015, 28(6): 401-405. DOI: 10.3969/j.issn.2095-9346.2015.06.001.

MOON J H, CHO C H, SON G H, et al . Advanced circadian phase in mania and delayed circadian phase in mixed mania and depression returned to normal after treatment of bipolar disorder[J ] . EBioMedicine, 2016, 11: 285-295. DOI: 10.1016/j.ebiom.2016.08.019.

MOREIRA J, GEOFFROY P A. Lithium and bipolar disorder: impacts from molecular to behavioural circadian rhythms[J]. Chronobiol Int, 2016, 33(4): 351-373. DOI: 10.3109/07420528.2016.1151026.

TAKAHASHI J S. Molecular components of the circadian clock in mammals[J]. Diabetes Obes Metab, 2015, 17 Suppl 1(0 1): 6-11. DOI: 10.1111/dom.12514.

CHARRIER A, OLLIAC B, ROUBERTOUX P, et al . Clock genes and altered sleep-wake rhythms: their role in the develop ment of psychiatric disorders[J ] . Int J Mol Sci, 2017, 18(5): 938. DOI: 10.3390/ijms18050938.

YEGIN Z, SARISOY G, ERGUNER ARAL A, et al . For whom the circadian clock ticks? Investigation of PERIOD and CLOCK gene variants in bipolar disorder[J ] . Chronobiol Int, 2021, 38(8): 1109-1119. DOI: 10.1080/07420528.2021.1917594.

LANDGRAF D, JOINER W J, MCCARTHY M J, et al . The mood stabilizer valproic acid opposes the effects of dopamine on circadian rhythms[J ] . Neuropharmacology, 2016, 107: 262-270. DOI: 10.1016/j.neuropharm.2016.03.047.

MACIUKIEWICZ M, DMITRZAK-WEGLARZ M, PAWLAK J, et al . Analysis of genetic association and epistasis interactions between circadian clock genes and symptom dimensions of bipolar affective disorder[J ] . Chronobiol Int, 2014, 31(6): 770-778. DOI: 10.3109/07420528.2014.899244.

MCCARTHY M J, WEI H, MARNOY Z, et al . Genetic and clinical factors predict lithium's effects on PER2 gene expression rhythms in cells from bipolar disorder patients[J ] . Transl Psychiatry, 2013, 3(10): e318. DOI: 10.1038/tp.2013.90.

MORIYA S, TAHARA Y, SASAKI H, et al . Effect of quetiapine on Per1, Per2, and Bmal1 clock gene expression in the mouse amygdala and hippocampus[J ] . J Pharmacol Sci, 2014, 125(3): 329-332. DOI: 10.1254/jphs.14071sc.

姚若松, 梁乐瑶. 大五人格量表简化版(NEO-FFI)在大学生人群的应用分析[J]. 中国临床心理学杂志, 2010, 18(4): 457-459.

YAO R S, LIANG L Y. Analysis of the application of simplified NEO-FFI to undergraduates[J]. Chin J Clin Psychol, 2010, 18(4): 457-459.

SHI YY, HE L. Shesis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci[J]. Cell Res, 2005, 15(2): 97-98. DOI: 10.1038/sj.cr.7290272.

BEDONT J L, IASCONE D M, SEHGAL A. The lineage before time: circadian and nonclassical clock influences on development[J]. Annu Rev Cell Dev Biol, 2020, 36: 469-509. DOI: 10.1146/annurev-cellbio-100818-125454.

SCHIBLER U. BMAL1 dephosphorylation determines the pace of the circadian clock[J]. Genes Dev, 2021, 35(15/16): 1076-1078. DOI: 10.1101/gad.348801.121.

RAKSHIT K, MATVEYENKO A V. Induction of core circadian clock transcription factor Bmal1 enhances β-cell function and protects against obesity-induced glucosein tolerance[J]. Diabetes, 2021, 70(1): 143-154. DOI: 10.2337/db20-0192.

WANG NN, YANG G R, JIA Z J, et al . Vascular PPARgamma controls circadian variation in blood pressure and heart rate through Bmal 1[J ] . Cell Metab, 2008, 8(6): 482-491. DOI: 10.1016/j.cmet.2008.10.009.

BABA K, PIANO I, LYUBOSLAVSKY P, et al . Removal of clock gene Bmal1 from the retina affects retinal development and accelerates cone photoreceptor degeneration during aging[J ] . Proc Natl Acad Sci USA, 2018, 115(51): 13099-13104. DOI: 10.1073/pnas.1808137115.

LEE S B, PARK J, KWAK Y, et al . Disrupted-in-schizophrenia 1 enhances the quality of circadian rhythm by stabilizing BMAL1[J ] . Transl Psychiatry, 2021, 11(1): 110. DOI: 10.1038/s41398-021-01212-1.

QIU P Y, JIANG J, LIU Z, et al . BMAL1 knockout macaque monkeys display reduced sleep and psychiatric disorders[J ] . Natl Sci Rev, 2019, 6(1): 87-100. DOI: 10.1093/nsr/nwz002.

VON SCHANTZ M, LEOCADIO-MIGUEL M A, MCCARTHY M J, et al . Genomic perspectives on the circadian clock hypothesis of psychiatric disorders[J ] . Adv Genet, 2021, 107: 153-191. DOI: 10.1016/bs.adgen.2020.11.005.

BARNETT J H, HUANG J, PERLIS R H, et al . Personality and bipolar disorder: dissecting state and trait associations between mood and personality[J ] . Psychol Med, 2011, 41(8): 1593-1604. DOI: 10.1017/S0033291710002333.

刘畅畅, 陈方煜, 戴媛媛, 等. 人格特质及家庭功能对双相情感障碍患者冲动性的影响分析[J]. 精神医学杂志, 2021, 34(5): 432-435. DOI: 10.3969/j.issn.2095-9346.2021.05.010.

LIU C C, CHEN F Y, DAI Y Y, et al . The influences of personality trait and family function on impulsivity in patients with bipolar disorder[J ] . J Psychiatry, 2021, 34(5): 432-435. DOI: 10.3969/j.issn.2095-9346.2021.05.010.

孙继伟, 李佳欢, 王艳荣, 等. 烧伤康复期患者神经质人格、心理弹性与创伤后应激障碍症状和创伤后成长之间的关系[J]. 中国心理卫生杂志, 2019, 33(3): 198-202. DOI: 10.3969/j.issn.1000-6729.2019.03.008.

SUN J W, LI J H, WANG Y R, et al. Relation of neuroticism and resilience to posttraumatic stress disorder and post-traumatic growth in patients with burns during rehabilitation[J ] . Chin Ment Heal J, 2019, 33(3): 198-202. DOI: 10.3969/j.issn.1000-6729.2019.03.008.

杨道良, 刘寒, 吴宇杰, 等. 双相障碍患者攻击行为与DRD4基因多态性及人格特征的关联研究[J]. 上海交通大学学报(医学版), 2020, 40(3): 362-367. DOI: 10.3969/j.issn.1674-8115.2020.03.014.

YANG D L, LIU H, WU Y J, et al . Relationship between aggressive behavior in patients with bipolar disorder and DRD4 gene polymorphism and personality characteristics[J ] . J Shanghai Jiaotong Univ Med Sci, 2020, 40(3): 362-367. DOI: 10.3969/j.issn.1674-8115.2020.03.014.

HUANG C C, LU R B, YEN C H, et al . Dopamine transporter gene may be associated with bipolar disorder and its personality traits[J ] . Eur Arch Psychiatry Clin Neurosci, 2015, 265(4): 281-290. DOI: 10.1007/s00406-014-0570-0.

LESZCZYŃSKA-RODZIEWICZ A, MACIUKIEWICZ M, SZCZEPANKIEWICZ A, et al . Association between OPCRIT dimensions and polymorphisms of HPA axis genes in bipolar disorder[J ] . J Affect Disord, 2013, 151(2): 744-747. DOI: 10.1016/j.jad.2013.08.012.

KRISHNA V N, THUNGA R, UNNIKRISHNAN B, et al . Association between bipolar affective disorder and thyroid dysfunction[J ] . Asian J Psychiatr, 2013, 6(1): 42-45. DOI: 10.1016/j.ajp.2012.08.003.

粟幼嵩, 陈俊, 洪武, 等. 以抑郁或躁狂首次发病的双相障碍患者临床特征及甲状腺功能水平回顾性分析[J]. 中华精神科杂志, 2016, 49(1): 42-46. DOI: 10.3760/cma.j.issn.1006-7884.2016.01.011.

SU Y S, CHEN J, HONG W, et al . A comparative study of the clinical features and thyroxine levels between bipolar patients with different first onset types[J ] . Chin J Psychiatry, 2016, 49(1): 42-46. DOI: 10.3760/cma.j.issn.1006-7884.2016.01.011.

石磊. 甲状腺功能水平与双相情感障碍相关性比较分析[J]. 中西医结合心血管病电子杂志, 2017, 5(10): 13-14. DOI: 10.16282/j.cnki.cn11-9336/r.2017.10.008.

SHI L. Comparative analysis of correlation between thyroid function level and bipolar disorder[J]. Cardiovasc Dis J Integr Tradit Chin West Med, 2017, 5(10): 13-14. DOI: 10.16282/j.cnki.cn11-9336/r.2017.10.008.

ZIV-GAL A, FLAWS J A, MAHONEY M M, et al . Genetic polymorphisms in the aryl hydrocarbon receptor-signaling pathway and sleep disturbances in middle-aged women[J ] . Sleep Med, 2013, 14(9): 883-887. DOI: 10.1016/j.sleep.2013.04.007.

HAHN J, GVNTER M, SCHUHMACHER J, et al . Sleep enhances numbers and function of monocytes and improves bacterial infection outcome in mice[J ] . Brain Behav Immun, 2020, 87: 329-338. DOI: 10.1016/j.bbi.2020.01.001.

BENGESSER S A, HOHENBERGER H, TROPPER B, et al . Gene expression analysis of MAOA and the clock gene ARNTL in individuals with bipolar disorder compared to healthy controls[J ] . World J Biol Psychiatry, 2021. DOI: 10.1080/15622975.2021.1973816.

刘磊, 陈贻华, 蒋廷云, 等. 中山市双相情感障碍住院患者临床特征和诊断变化趋势的回顾性调查[J]. 齐齐哈尔医学院学报, 2019, 40(5): 611-613. DOI: 10.3969/j.issn.1002-1256.2019.05.035.

LIU L, CHEN Y H, JIANG T Y, et al. A retrospective study of clinical features and factors related with diagnosis changes in inpatients with bipolar disorder in Zhongshan City[J ] . J Qiqihar Med Univ, 2019, 40(5): 611-613. DOI: 10.3969/j.issn.1002-1256.2019.05.035.

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BMAL1基因单核苷酸多态性与双相情感障碍的关联性研究

Association between single nucleotide polymorphism of BMAL1 and bipolar disorder

DOI：10.16016/j.2097-0927.202203131

摘要

Abstract

关键词

Keywords

references