Interaction between 5-hydroxytryptamine receptor 1B gene and serotonin transporter gene is potentially associated with suicide attempts in youths

Wei LIU; Liuyi RAN; Jiajia JIN; Suya WANG; Tong WU; Ming AI; Jianmei CHEN; Li KUANG

doi:10.16016/j.1000-5404.201711199

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Interaction between 5-hydroxytryptamine receptor 1B gene and serotonin transporter gene is potentially associated with suicide attempts in youths

Clinical Medicine | 更新时间：2026-01-09

- Interaction between 5-hydroxytryptamine receptor 1B gene and serotonin transporter gene is potentially associated with suicide attempts in youths
- Journal of Third Military Medical University Vol. 40, Issue 12, Pages: 1115-1119(2018)
- 作者机构：
  
  1.401331 重庆，重庆医科大学附属大学城医院心理卫生中心
  2.400016重庆，重庆医科大学附属第一医院心理卫生中心
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81671360)
- DOI：10.16016/j.1000-5404.201711199
  CLC： R181.23;R394.1;R395.6
- Received：23 November 2017，
  
  Revised：2018-03-15，
  
  Published：2018-01
- 稿件说明：
移动端阅览
Wei LIU, Liuyi RAN, Jiajia JIN, et al. Interaction between 5-hydroxytryptamine receptor 1B gene and serotonin transporter gene is potentially associated with suicide attempts in youths[J]. Journal of Third Military Medical University, 2018, 40(12): 1115-1119.
DOI：

Wei LIU, Liuyi RAN, Jiajia JIN, et al. Interaction between 5-hydroxytryptamine receptor 1B gene and serotonin transporter gene is potentially associated with suicide attempts in youths[J]. Journal of Third Military Medical University, 2018, 40(12): 1115-1119. DOI： 10.16016/j.1000-5404.201711199.

摘要

目的

探讨五羟色胺(5-hydroxy tryptamine，5-HT)系统中五羟色胺1B受体(5-hydroxy tryptamine 1B receptor，5-HTR1B)基因和五羟色胺转运体(5-hydroxy tryptamine transporter，5-HTT)基因的交互作用对青年人自杀未遂行为的影响。

方法

选取5-HTR1B基因rs6296和5-HTT基因rs1042173、rs140701、rs2066713多态性位点，采用iMLDRTM多重SNP分型技术对病例组(70例自杀未遂青年人)和对照组(112例健康青年人)进行检验。采用广义多因子降维法(generalized multifactor dimensionality reduction，GMDR)分析基因-基因交互作用。

结果

5-HTT基因rs1042173、rs140701、rs2066713的基因型频率和等位基因频率在病例组和对照组中分布差异无统计学意义(

0.05)。5-HTR1B rs6296等位基因频率在病例组和对照组中分布差异无统计学意义(

0.05)，5-HTR1B rs6296病例组基因型频率(CC 31.4%、CG 31.4%、GG 37.1%)和对照组基因型频率(CC 19.8%、CG 53.2%、GG 27%)分布差异有统计学意义(χ

=8.327，

=0.016)，经Bonferroni校正后差异无统计学意义(

0.05)。GMDR分析结果显示，5-HTT与5-HTR1B基因交互作用存在于两位点模型(rs1042173、rs6296，测试样本精确度0.6185，交叉验证一致性10/10，

值为0.0210~0.0220)、三位点模型(rs1042173、rs140701、rs6296，测试样本精确度0.644 5，交叉验证一致性10/10，

值为0.003 0~0.004 0)、四位点模型(rs1042173、rs140701、rs2066713、rs6296，测试样本精确度0.6120，交叉验证一致性9/10，

值为0.0320~0.0330)。

结论

5-HTR1B和5-HTT基因存在交互作用，并可能与青年人的自杀未遂行为有关。

Abstract

Objective

To explore the interaction between 5-hydroxytryptamine (5-HT) receptor 1B (5-HTR1B) gene and 5-HT transporter (5-HTT) gene in the 5-HT system and investigate how this interaction is associated with attempted suicide in youths.

Methods

iMLDRTM multiplex single nucleotide polymorphism (SNP) typing was used to examine the SNPs at one locus (rs6296) of 5-HTR1B gene and 3 loci (rs1042173

rs140701 and rs2066713) of 5-HTT gene in 70 youths (aged 15-24 years) with attempted suicide (case group) and 112 age-matched healthy subjects (control group). The interaction between 5-HTR1B gene and 5-HTT gene was analyzed using generalized multifactor dimensionality reduction (GMDR).

Results

No significant differences were found between the case and control groups in the genotype frequencies or allele frequencies at the loci rs1042173

rs140701

or rs2066713 in 5-HTT gene (

0.05). The allele frequency of rs6296 in 5-HTR1B gene was similar between the 2 groups (

0.05)

but the CC

and GG genotype frequencies of 5-HTR1B rs6296 differed significantly between the case group (31.4%

31.4%

and 37.1%

respectively) and the control group (19.8%

53.2%

and 27%

respectively) (

Chi

-square=8.327

=0.016); these differences

however

were not statistically significant after Bonferroni correction (

0.05). GMDR analysis indicated the presence of interactions between 5-HTT gene and 5-HTR1B gene in the two-site model (rs1042173 and rs6296) with a test accuracy of 0.6185 and a cross validation consistency of 10/10 (

=0.021 0-0.022 0)

in the three-site model (rs1042173

rs140701

and rs6296) with a test accuracy of 0.644 5 and cross validation consistency of 10/10 (

=0.0030-0.0040) as well as in the four-site model (rs1042173

rs140701

rs2066713

and rs6296) with a test accuracy of 0.6120 and a cross validation consistency of 10/10 (

=0.0320-0.0330).

Conclusion

There are interactions between 5-HTR1B gene and 5-HTT gene

which may be associated with attempted suicide in youths.

关键词

Keywords

references

[World Health Organization (2014). WHO methods and data sources for global causes of death 2000 2012[EB/OL ] . Global Health Estimates Technical Paper WHO/HIS/HSI/GHE/2014. 7. http://www.who.int/healthinfo/global_burden_disease/GlobalCOD_method_2000_2012.pdf?ua=1 http://www.who.int/healthinfo/global_burden_disease/GlobalCOD_method_2000_2012.pdf?ua=1 .

MIRKOVIC B, LAURENT C, PODLIPSKI M A, et al . Genetic association studies of suicidal behavior: A review of the past 10 years, progress, limitations, and future directions[J ] . Front Psychiatry, 2016, 7: 158. DOI: 10.3389/fpsyt.2016.00158.

BRENT D A, BRIDGE J, JOHNSON B A, et al . Suicidal behavior runs in families. A controlled family study of adolescent suicide victims[J ] . Arch Gen Psychiatry, 1996, 53(12): 1145-1152. DOI:10.1001/archpsyc.1996.018301 2085015.

CHO H, GUO G, IRITANI B J, et al . Genetic contribution to suicidal behaviors and associated risk factors among adolescents in the U.S.A[J ] . Prev Sci, 2006, 7(3): 303-311. DOI: 10.1007/s11121-006-0042-5.

ALTHOFF R R, HUDZIAK J J, WILLEMSEN G, et al . Genetic and environmental contributions to self-reported thoughts of self-harm and suicide[J ] . Am J Med Genet B Neuropsychiatr Genet, 2012, 159B(1): 120-127. DOI: 10.1002/ajmg.b.32010.

VORACEK M, LOIBL L M. Genetics of suicide: a systematic review of twin studies[J]. Wien Klin Wochenschr, 2007, 119(15-16): 463-475. DOI: 10.1007/s00508-007-0823-2.

ANTYPA N, SERRETTI A, RUJESCU D. Serotonergic genes and suicide: a systematic review[J]. Eur Neuropsychophar macol, 2013, 23(10): 1125-1142. DOI: 10.1016/j.euroneuro. 2013.03.013.

KRANZLER H R, HERNANDEZ-AVILA C A, GELERNTER J. Polymorphism of the 5-HT1B receptor gene (HTR1B): strong within-locus linkage disequilibrium without association to antisocial substance dependence[J]. Neuropsychopharmacology, 2002, 26(1): 115-122. DOI:10.1016/S0893-133X (01)00283-4.

NEVES F S, MALLOY-DINIZ L F, ROMANO-SILVA M A, et al . Is the serotonin transporter polymorphism (5-HTTLPR) a potential marker for suicidal behavior in bipolar disorder patients[J ] . J Affect Disord, 2010, 125(1-3): 98-102. DOI: 10.1016/j.jad.2009.12.026.

BUTTENSCH N H N, FLINT T J, FOLDAGER L, et al . An association study of suicide and candidate genes in the serotonergic system[J ] . J Affect Disord, 2013, 148(2-3): 291-298. DOI: 10.1016/j.jad.2012.12.011.

MONTASSER M E, ZIV-GAL A, BROWN J P, et al . A potentially functional variant in the serotonin transporter gene is associated with premenopausal and perimenopausal hot flashes[J ] . Menopause, 2015, 22(1): 108-113. DOI: 10.1097/GME.0000000000000291.

PANDEY G N, DWIVEDI Y, RIZAVI H S, et al . Higher expression of serotonin 5-HT(2A) receptors in the postmortem brains of teenage suicide victims[J ] . Am J Psychiatry, 2002, 159(3): 419-429. DOI: 10.1176/appi.ajp.159.3.419.

PANDEY G N, DWIVEDI Y, REN X, et al . Brain region specific alterations in the protein and mRNA levels of protein kinase A subunits in the post-mortem brain of teenage suicide victims[J ] . Neuropsychopharmacology, 2005, 30(8): 1548-1556. DOI: 10.1038/sj.npp.1300765.

PANDEY G N, REN X, RIZAVI H S, et al . Brain-derived neurotrophic factor and tyrosine kinase B receptor signalling in post-mortem brain of teenage suicide victims[J ] . Int J Neuropsychopharmacol, 2008, 11(8): 1047-1061. DOI: 10.1017/S1461145708009000.

操军, 艾明, 况利, 等.重庆市大学生自杀未遂及其影响因素的调查分析[J].第三军医大学学报, 2013, 35(24): 2692-2696.

CAO J, AI M, KUANG L, et al . Survey on suicide attempts and influencing factors of college students in Chongqing[J ] . J Third Mil Med Univ, 2013, 35(24): 2692-2696.

ASBERG M, TR SKMAN L, THOR N P. 5-HIAA in the cerebrospinal fluid. A biochemical suicide predictor[J]. Arch Gen Psychiatry, 1976, 33(10): 1193-1197.

MURPHY T M, RYAN M, FOSTER T, et al . Risk and protective genetic variants in suicidal behaviour: association with SLC1A2, SLC1A3, 5-HTR1B & NTRK2 polymorphisms[J ] . Behav Brain Funct, 2011, 7: 22. DOI: 10.1186/1744- 9081-7-22.

HSU Y F, CHEN P F, LUNG F W. Parental bonding and personality characteristics of first episode intention to suicide or deliberate self-harm without a history of mental disorders[J]. BMC Public Health, 2013, 13: 421. DOI: 10.1186/1471-2458-13-421.

HUNG C F, LUNG F W, CHEN C H, et al . Association between suicide attempt and a tri-allelic functional polymorphism in serotonin transporter gene promoter in Chinese patients with schizophrenia[J ] . Neurosci Lett, 2011, 504(3): 242-246. DOI: 10.1016/j.neulet.2011.09.036.

SENEVIRATNE C, HUANG W, AIT-DAOUD N, et al . Characterization of a functional polymorphism in the 3' UTR of SLC6A4 and its association with drinking intensity[J ] . Alcohol Clin Exp Res, 200 9, 33(2): 332-339. DOI: 10.1111/j.1530-0277.2008.00837.x.

WILLOUR V L, SEIFUDDIN F, MAHON P B, et al . A genome-wide association study of attempted suicide[J ] . Mol Psychiatry, 2012, 17(4): 433-444. DOI: 10.1038/mp.2011.4.

RITCHIE M D, HAHN L W, ROODI N, et al . Multifactor-dimensionality reduction reveals high-order interactions among estrogen-metabolism genes in sporadic breast cancer[J ] . Am J Hum Genet, 2001, 69(1): 138-147. DOI: 10.1086/321276.

LOU X Y, CHEN G B, YAN L, et al . A generalized combinatorial approach for detecting gene-by-gene and gene-by-environment interactions with application to nicotine dependence[J ] . Am J Hum Genet, 2007, 80(6): 1125-1137. DOI: 10.1086/518312.

HU G, YANG C, ZHAO L, et al . The interaction of NOS1AP, DISC1, DAOA, and GSK3B confers susceptibility of early-onset schizophrenia in Chinese Han population[J ] . Prog Neuropsychopharmacol Biol Psychiatry. 2018, 81(2): 187-193. DOI: 10.1016/j.pnpbp.2017.10.017.

LESZCZYŃSKA-RODZIEWICZ A, SZCZEPANKIEWICZ A, PAWLAK J, et al . Association, haplotype, and gene-gene interactions of the HPA axis genes with suicidal behaviour in affective disorders[J ] . Sci World J, 2013, 2013: 207361. DOI: 10.1155/2013/207361.

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