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- 2018
自杀行为中5-HT基因和GAD1基因的交互作用
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Abstract:
摘要：目的 初步探讨5-羟色胺受体2C(5-HTR2C)基因、单胺氧化酶A(MAOA)基因和谷氨酸脱羧酶(GAD1)基因多态性与自杀行为的关系，并分析基因-基因之间的交互作用。方法 对中国人群中21例有自杀行为史病例样本和50例健康对照者进行基因型分型；采用多因子降维法进行交互作用分析。结果 对照组符合哈温平衡(HWE)检验，病例组中5-HTR2C位点不符合HWE检验(P<0.05)，经过性别矫正检验显示与自杀行为正相关；两组的5-HTR2C基因型频率差别有统计学意义(χ2=6.18，P=0.04)；病例组和对照组MAOA、GAD1基因型频数差异均无显著统计学意义(P>0.05)。在MDR模型分析得到最优模型组合为rs5953210-rs769391位点构建的交互模型OR=20.19，95% CI 4.19～97.38，P<0.01，交互作用显著。结论 5-HTR2C 基因rs3813928、rs518147位点多态性可能与自杀行为存在关联，与GAD1基因rs3749034、rs769391位点和MAOA基因rs5953210、rs979605位点无关联。在MDR模型中，5-HTR2C 基因与MAOA基因在自杀行为发病中具有显著交互效应，可增加自杀行为的发病风险。
ABSTRACT: Objective To investigate gene-gene interactions of suicidal behavior with single-nucleotide-polymorphism (SNP) in MAOA, GAD1 and 5-HTR2C by multifactor dimensionality reduction. Methods For this case-control study, six SNPs were captured in related genes and detected in blood samples obtained from 21 patients with suicidal behavior and 50 healthy individuals. The genotype frequency and allele frequency as well as the Hardy-Weinberg equilibrium (HWE), tests were performed and compared by plink software. The gene-gene interactions models were built by the MDR software. Results The HWE test for case group showed that rs3813928 rs518147 of 5-HTR2C gene was not in line with HWE (P<0.05). However, the additive model analysis after adjustment by gender indicated that the polymorphism had a positive correlation with suicidal behavior in case group. The case and control groups differed significantly only in genotype frequencies of 5-HTR2C gene (χ2=6.18, P=0.04). There was no significant difference in allele and genotype frequencies of the other genes (P>0.05). The best combination model of MDR was rs5953210-rs769391 OR=20.19, 95% CI 4.19-97.38, P<0.01, with significant interaction. Conclusion The 5-HTR2C gene rs3813928 and rs518147 polymorphisms may play an important role in the susceptibility to suicidal behavior. The combination of MAOA with GAD1 has a significant interaction which may increase the risk of suicidal behavior
| [1] | KOLLA NJ, CHIUCCARIELLO L, WILSON AA, et al. Elevated monoamine oxidase-A distribution volume in borderline personality disorder is associated with severity across mood symptoms, suicidality, and cognition[J]. Biol Psychiatry, 2016, 79(2):117-126. |
| [2] | YUCEL Y, COSKUN S, CENGIZ B, et al. Association of polymorphisms within the serotonin receptor genes 5-HTR1A, 5-HTR1B, 5-HTR2A and 5-HTR2C and migraine susceptibility in a Turkish population[J]. Clin Psychopharmacol Neurosci, 2016, 14(3):250-255. |
| [3] | BRUMMETT BH, BABYAK MA, WILLIAMS RB, et al. A putatively functional polymorphism in the HTR2C gene is associated with depressive symptoms in white females reporting significant life stress[J]. PLoS One, 2014, 9.12. |
| [4] | THELMA BEATRIZ GC, ISELA R, ALMA G, et al. Association between 5-HTR2C gene variants and suicidal behaviour: A protocol for the systematic review and meta-analysis of genetic studies[J]. BMJ Open, 2014. 4(9):e005423. |
| [5] | BANLAKI Z, ELEK Z, NANASI T, et al. Polymorphism in the serotonin receptor 2a (HTR2A) gene as possible predisposal factor for aggressive traits [J]. PLoS One, 2015, 10(2):e0117792. |
| [6] | DE LUCA V, THARMALIGAN S, STRAUSS J, et al. 5-HT2C receptor and MAO-A interaction analysis: No association with suicidal behaviour in bipolar patients[J]. Eur Arch Psychiatry Clin Neurosci, 2008, 258(7):428-433. |
| [7] | MANN JJ, OQUENDO MA, WATSON KT, et al. Anxiety in major depression and cerebrospinal fluid free gamma-aminobutyric acid[J]. Depress Anxiety, 2014, 31(10):814-821. |
| [8] | SOKOLOWSKI M, BEN YJ, WASSERMAN J, et al. Glutamatergic GRIN2B and polyaminergic ODC1 genes in suicide attempts: associations and gene-environment interactions with childhood/adolescent physical assault[J]. Mol Psychiatry, 2013, 18(9):985-992. |
| [9] | DONALDSON ZR, NAUTIYAL KM, AHMARI SE, et al. Genetic approaches for understanding the role of serotonin receptors in mood and behavior[J]. Curr Opin Neurobiol, 2013, 23(3):399-406. |
| [10] | 俞琼，付颖利，冯佳，等. 5-羟色胺1A受体基因多态性与自杀关联性的Meta分析[J]. 吉林大学学报(医学版), 2010, 36(3):1134-1137. |
| [11] | ANTYPA N, SERRETTI A, DAN R, et al. Serotonergic genes and suicide: A systematic review[J]. Eur Neuropsychopharmacol, 2013, 23(10):1125-1142. |
| [12] | ANDREOU D, SODERMAN E, AXELSSON T, et al. Polymorphisms in genes implicated in dopamine, serotonin and noradrenalin metabolism suggest association with cerebrospinal fluid monoamine metabolite concentrations in psychosis[J]. Behav Brain Funct, 2014, 10:26. |
| [13] | LI CF, LUO FT, ZENG YX, et al. Weighted risk score-based multifactor dimensionality reduction to detect gene-gene interactions in nasopharyngeal carcinoma[J]. Int J Mol Sci, 2014，15(6): 10724-10737. |
| [14] | 袁芳，刘盼盼，徐进，等. 基因-基因(环境)交互作用分析方法的比较[J]. 宁波大学学报(理工版), 2012, 25(4):115-119. |
| [15] | QUILTER CR, BAGGA M, MOINIE A, et al. Gene structure and expression of serotonin receptor 5-HTR2C in hypothalamic samples from infanticidal and control sows[J]. BMC Neurosci, 2012, 13:37. |
| [16] | CERVERA-JUANES R, WILHEM LJ, PARK B, et al. MAOA expression predicts vulnerability for alcohol use[J]. Mol Psychiatry, 2016, 21(4):472-479. |
| [17] | FAN M, LIU B, JIANG X, et al. Meta-analysis of the association between the monoamine oxidase-A gene and mood disorders [J]. Psychiatr Genet, 2010, 20(1):1-7. |
| [18] | LUNG FW, TZENG DS, HUANG MF, et al. Association of the MAOA promoter uVNTR polymorphism with suicide attempts in patients with major depressive disorder[J]. BMC Med Genet, 2011, 12:74. |
| [19] | TAO R, DAVIS KN, LI C, et al. GAD1 alternative transcripts and DNA methylation in human prefrontal cortex and hippocampus in brain development, schizophrenia[J]. Mol Psychiatry, 2017，105. |
| [20] | BARBON A, ORLANDI C, LA VL, et al. Antidepressant treatments change 5-HT2C receptor mRNA expression in rat prefrontal/frontal cortex and hippocampus[J]. Neuropsychobiology, 2011, 63(3):160-168. |
| [21] | SMILEY JF, HACKEET TA, BLEIWAS C, et al. Reduced GABA neuron density in auditory cerebral cortex of subjects with major depressive disorder[J]. J Chem Neuroanat, 2016, 76(Pt B):108-121. |
| [22] | ASAOKA N, NISHITANI N, KINOSHITA H, et al. Chronic antidepressant potentiates spontaneous activity of dorsal raphe serotonergic neurons by decreasing GABAB receptor-mediated inhibition of L-type calcium channels[J]. Sci Rep, 2017, 7(1):13609. |
| [23] | GATTONE PM. Preventing death by suicide[J]. Epilepsy Behav, 2016, 61:292-293. |
| [24] | DAVIS KN, TAO R, LI C, et al. GAD2 alternative transcripts in the human prefrontal cortex, and in schizophrenia and affective disorders[J]. PLoS One, 2016, 11(2):e0148558. |
| [25] | 颜因，曹莉莎，李敏，等. 氟西汀作用于慢性温和不可预见性应激大鼠海马组织前后的差异蛋白质组学研究[J]. 川北医学院学报, 2016, 31(3):336-341. |
