HTR3A及HTR3B Tag SNP与中国汉族双相障碍及其认知功能的关联研究
发布时间：2018-07-18 10:48
【摘要】：目的：检测HTR3A及HTR3B的21个标记单核苷酸多态(tag SNP)在患者及对照者的等位基因及基因型分布,通过病例-对照关联研究探讨双相障碍遗传易感性,寻找双相障碍的易感基因,探讨HTR3A及HTR3BTag SNP基因多态性、遗传不平衡性及单倍型与双相障碍患者疾病特点及认知功能的关联性,进一步验证认知功能损害是否为双相障碍的内表型特征,为理论研究及临床实践提供重要的参考依据,为双相障碍早期识别提供理论依据。方法：病例组研究对象来自2013年6月-2015年5月在山东省精神卫生中心住院的209例双相障碍患者,包括双相障碍Ⅰ型患者107例,双相Ⅱ型患者102例。健康对照组为200例同期招募的健康对照者。收集5m1EDTA抗凝血,采用QIAamp全血DNA试剂盒提取基因组DNA。经飞行质谱(MALDI-TOF)Sequenom MassArray平台进行基因分型,采用PLINK1.07及SPSS20.0统计软件进行卡方检验及回归分析等并对分型成功且符合H-W平衡的SNP进行关联分析研究,计算OR值及p值。通过Haploview4.2计算连锁不平衡性,构建HTR3A及HTR3B单倍型,验证HTR3A、HTR3B的多态性位点与中国汉族双相障碍易感性的关联性。对符合入组标准的双相障碍患者,采集病例组疾病资料包括家族史、起病年龄,发作次数及有无精神病性症状等。对病例组及健康对照组入组1周内完成认知功能成套测验(包括连线测验、符号编码、言语流畅性、词语学习、视觉空间记忆、迷宫测验、stroop色词测验及持续操作测验等)评估,分析HTR3A及HTR3B Tag SNP与双相障碍认知功能损害的关联性。结果：1.基因频率及基因型频率结果显示HTR3A的位点rs1062613的T等位基因、rs1176722的A等位基因、rs1176719的A等位基因、rs10160548的G等位基因及rs1176713的C等位基因.HTR3B一个多态性位点rs1176746的T等位基因在病例组及对照组之间的差异性具统计学意义(p0.05)。HTR3A及HTR3B标记多态位点在病例组与对照组的基因型比较结果显示,HTR3A的rsl 176722、rs1176719、rs10160548及rs1176713位点及HTR3B的位点rs1176746携带突变基因型的患者个体例数显著高于野生纯合基因型个体例数,差异性具统计学意义(p005)。2.单倍型分析结果显示HTR3A及HTR3B的16个位点成功构建与双相障碍易感性相关联的3个单倍体,HTR3B的单倍型rs4938056：T,rs12421126：T,rs1176746：C,rs1176744：G,rs2276305：G,rs3782025：T,rs1672717：T,rs12795805：C与双相障碍发病的关联性具有显著意义(p0.05),分层分析结果显示,双相障碍Ⅰ型也构建了3个单倍体,由HTR3A的5个多态性位点rs1062613、rs11604247、rs1176722、rs2276302及rs1176719组成的CCGAG、CCGAA这2种单倍型基因频率在双相障碍Ⅰ型与对照组间比较有统计学意义(p005),双相障碍Ⅱ型构建了4个单倍体,各单倍型与对照组比较不具有统计学意义(p0.05)。3.双相障碍临床特点与HTR3A及HTR3B标记多态性位点基因型的关联分析结果显示HTR3A的rs11604247、rs2276302、rs10160548、rs1182457携带突变基因个体存在精神病性症状的比例较野生纯合患者个体显著增多(p0.05),携带HTR3A的rs1062613突变基因个体存在精神病性症状的比例较野生纯合患者个体显著减少(p0.05),HTR3B除rsl672717及rs12795805以外的九个位点均与双相障碍精神病性症状存在显著关联性,其中rs10789970、rs3831455、rs4938056、rsl2421126、rs1176746及rs3782025这六个位点的突变基因个体存在精神病性症状的比例较野生纯合患者个体显著增多(p0.05),位点rs3758987、rs1176744及rs2276305突变基因个体存在精神病性症状的比例较野生纯合患者个体显著减少(p0.05)。HTR3A的位点rs10160548、rs1176713及HTR3B的位点rs4938056、rs3782025及rs1672717携带突变基因的基因型组的平均起病年龄均较野生纯合基因型组的平均起病年龄早,具有统计学意义(p0.05),HTR3B位点rs1176746携带突变基因的基因型组的平均起病年龄均较野生纯合基因型组的平均起病年龄晚,差异性显著(p0.05)。HTR3A多数多态性位点携带突变基因的基因型组的平均病程均纯合野生基因型组的平均病程长,其中rs1062613及rs10789980这两个位点在两组之间的差异性有统计学意义(p0.05),HTR3B除三个位点(rs1176744、rs2276305及rs12795805)外的八个位点携带突变基因的基因型组的平均病程均较纯合野生基因型组的平均病程短,其中rs10789970、rs12421126及rs2276305这三个位点在两组之间的差异性有统计学意义(p0.05)。HTR3A的位点rs10789980与发作次数呈正相关(r=0.283,p0.01)位点rs1062613与家族史呈正相关(r=0.298,p0.01),HTR3A的其余位点与家族史及发作次数无显著相关性。HTR3B的的位点rs4938056及rs1176744与双相障碍家族史无显著相关性,rs12795805与家族史的相关系数(r=0.243,p005)稍低之外,其余八个多态性位点均与家族史呈显著相关性(r=0.262-0.424,p0.01)。HTR3B的多态性位点中,仅rs2276305与发作次数呈显著相关性(r=0.370,p0.01)。4.双相障碍病例组与对照组认知功能比较结果显示双相障碍Ⅰ型、双相障碍Ⅱ型及对照组三组在认知成套测验总分及各项认知测验T分的差异性均有统计学意义(F=4.525-8.539,p0.05)双相障碍Ⅰ型及双相障碍Ⅱ型各项认知测验得分均较对照组得分明显减少,组间比较结果除视觉空间记忆、持续操作测验及迷宫测试三项认知测验得分在双相障碍Ⅰ型与双相障碍Ⅱ型组间比较有统计学意义(p0.01)外,其余各项认知测验得分的组间差异性均无显著性统计学意义(p0.05)。双相障碍Ⅰ型与对照组比较结果显示,各项认知测验得分均有统计学意义(p0.05),而双相障碍Ⅱ型患者与对照组在信息处理速度、词语学习、工作记忆及社会认知这个四个认知领域的得分有统计学意义(p0.05),在视觉学习、注意/警觉性、推理/问题解决及认知测验总分这几个领域的差异性均无统计学意义。HTR3A及HTR3B基因多态性与双相障碍患者认知功能的关联研究结果显示,HTR3A大部分多态性位点携带突变基因的个体其认知功能测验得分较低,且在信息处理速度与注意/警觉性这两个认知领域的得分较野生基因型个体显著降低(p0..05)。HTR3A的rs1176722、rs2276302及rs1182457这三个标记多态性位点携带突变基因的个体其认知功能各领域均较野生纯合基因型个体显著减退(p0.05)。而HTR3B大部分多态性位点携带突变基因的个体其认知功能测验得分相对稍高,尤其在信息处理速度、工作记忆、注意／警觉性、社会认知这四个认知领域及总体认知功能较纯合野生基因型个体的认知功能相对受损较轻(p0.05),除rs10789970、rs2276305及rsl672717这三个多态性位点外,其余HTR3B的标记多态性位点携带突变基因的个体其认知功能各领域均较野生纯合基因型个体认知功能损害显著减轻(p0.05)。结论：1.HTR3A的rs1176722、rs1176719、rs10160548及rs1176713及HTR3B的rs1176746突变基因及突变基因型加大了双相障碍患者的发病风险。HTR3A的rs1062613的突变基因可能具有致病作用。2.由HTR3A的五个位点组成的CCGAG、CCGAA在双相障碍Ⅰ型的患者可能出现连锁遗传。双相障碍的患者中可能存在HTR3B的八个位点的连锁遗传。3.HTR3A个别位点及HTR3B多数位点基因多态性可能与双相障碍患者出现精神病性症状有关。HTR3A及HTR3B的个别位点基因多态性可能与双相障碍患者早年发病有关。HTR3A的多数位点突变基因可能与双相障碍患者病程延长有关。HTR3B多数位点突变基因分布可能增加了家族遗传的风险。HTR3A或HTR3B基因多态性与双相障碍发作次数无密切联系。4.双相障碍患者认知功能较健康对照者认知功能普遍下降。双相障碍Ⅰ型患者在信息处理速度、词语学习、工作记忆及社会认知领域的认知功能损害相对较重。HTR3A与加重双相障碍患者认知损害有关。HTR3B可能对减轻双相障碍患者认知功能损害有保护作用。5.信息处理速度、工作记忆、注意／警觉性、社会认知等领域的认知损害可能为双相障碍患者的内表型特征。
[Abstract]:Objective: to detect the allelic and genotype distribution of 21 labeled single nucleotide polymorphisms (tag SNP) of HTR3A and HTR3B in patients and controls, to explore the genetic susceptibility of bipolar disorder by case control association study and to search for the susceptibility genes of bipolar disorder, and to explore the polymorphism of HTR3A and HTR3BTag SNP genes, genetic imbalances and haplotypes and haplotypes. The relationship between the characteristics of disease and cognitive function in patients with bipolar disorder, further verifying whether cognitive impairment is an internal phenotype of bipolar disorder, provides an important reference for theoretical research and clinical practice, and provides a theoretical basis for the early recognition of bipolar disorder. Methods: the subjects of the case group were from May -2015 June 2013. 209 patients with bipolar disorder hospitalized in Shandong mental health center included 107 patients with bipolar type I and 102 biphasic type II patients. 200 healthy controls were recruited at the same time in the healthy control group. 5m1EDTA anticoagulant was collected, and QIAamp whole blood DNA kit was used to extract genomic DNA. via MALDI-TOF Sequenom MassArray level. The PLINK1.07 and SPSS20.0 statistical software were used to carry out the chi square test and regression analysis, and the SNP and the OR value and the p value were calculated. The OR value and the p value were calculated. The linkage disequilibrium was calculated by Haploview4.2 and the HTR3A and HTR3B single times were constructed to verify the HTR3A, HTR3B polymorphic loci and China. The correlation of the susceptibility to bipolar disorder in the Han nationality. For patients with bipolar disorder, the data included family history, age of onset, frequency of onset and symptoms of psychosis. The case group and healthy control group completed the cognitive function test (including connection test, symbol coding, speech flow) within 1 weeks. Unobstructed, verbal learning, visual spatial memory, maze test, Stroop Color Word Test and continuous operation test, and the correlation between the cognitive impairment of HTR3A and HTR3B Tag SNP and bipolar disorder. Results: the 1. gene frequency and genotype frequency results showed the T allele of the HTR3A site rs1062613, rs1176722 A allele, rs117 6719 A allele, rs10160548 G allele and rs1176713 C allele rs1176746 T allele between the case group and the control group were statistically significant (P0.05).HTR3A and HTR3B marker polymorphic loci in the case group and the control group, the results showed that HTR3A's 176722 The number of individual cases of rs1176719, rs10160548 and rs1176713 loci and HTR3B loci rs1176746 carrying mutant genotype was significantly higher than that of wild homozygous genotype, and the difference was statistically significant (P005).2. haplotype analysis showed that 16 sites of HTR3A and HTR3B were successfully constructed with 3 single links associated with the susceptibility to bipolar disorder. Ploidy, the association of HTR3B's haplotype rs4938056:T, rs12421126:T, rs1176746:C, rs1176744:G, rs2276305:G, rs3782025:T, rs1672717:T, and rs12795805:C was significant (P0.05). The stratified analysis showed that the biphasic disorder type I also constructed 3 haploidy, and the RS10 was 5 polymorphic loci of HTR3A. 62613, rs11604247, rs1176722, rs2276302 and rs1176719 composed of CCGAG, CCGAA, the frequency of the 2 haplotype genes was statistically significant (P005) between the two phase disorder type I and the control group (P005), and the biphasic barrier type II type had 4 haplotypes. The different haplotypes were not statistically significant (P0.05) the clinical characteristics of.3. biphasic disorder and HTR3. The correlation analysis between A and HTR3B markers showed that HTR3A rs11604247, rs2276302, rs10160548, the proportion of psychosis in rs1182457 carrying mutant genes increased significantly (P0.05) than those in the wild homozygous individuals (P0.05), and the proportion of psychotic symptoms in the individuals carrying HTR3A rs1062613 mutant genes was more wild than those in the wild. The patients with homozygous homozygous individuals decreased significantly (P0.05), and the nine loci other than rsl672717 and rs12795805 were significantly associated with bipolar disorder, and the proportion of individuals with rs10789970, rs3831455, rs4938056, rsl2421126, rs1176746 and rs3782025 in the six loci were more than the wild. Patients with homozygous individuals increased significantly (P0.05), the proportion of rs3758987, rs1176744 and rs2276305 mutant genes was significantly lower than those of the wild homozygous individuals (P0.05).HTR3A sites rs10160548, rs1176713 and HTR3B loci rs4938056, rs3782025, and rs1672717 carrying mutant genes. The age of the onset was earlier than the average age of the wild homozygous genotypic group (P0.05). The average onset age of the genotype group carrying the mutant gene in the HTR3B site rs1176746 was later than the average age of the wild homozygous genotype group, and the difference was significant (P0.05).HTR3A most polymorphic loci carrying the mutation gene. The average course of the homozygous wild genotypic group was long in the average course of the type group, and the difference between the two sites of rs1062613 and rs10789980 was statistically significant (P0.05), and the average course of the eight loci, except three loci (rs1176744, rs2276305 and rs12795805), was more than that of the homozygous group. The average course of the wild genotyping group was short, of which the three loci of rs10789970, rs12421126 and rs2276305 were statistically significant between the two groups (P0.05) the.HTR3A site rs10789980 was positively correlated with the number of episodes (r=0.283, P0.01) rs1062613 and family history (r=0.298, P0.01), the rest of the HTR3A sites and family history The site rs4938056 and rs1176744 had no significant correlation with the bipolar disorder family, and the correlation coefficient of rs12795805 and family history (r=0.243, P005) was slightly lower, and the other eight polymorphic loci were significantly correlated with family history (r= 0.262-0.424, P0.01).HTR3B (r= 0.262-0.424, P0.01).HTR3B, only rs227630. 5 a significant correlation with the frequency of seizures (r=0.370, P0.01).4. bipolar disorder case group and the control group compared with the control group, the results of cognitive function showed that the two phase obstacle type I, the two phase obstacle II and the control group three groups in the cognitive test total score and the difference of the cognitive test T scores were statistically significant (F=4.525-8.539, P0.05) biphasic disorder I type and The scores of each cognitive test of bipolar disorder type II were significantly lower than those of the control group. The scores of three cognitive tests, except visual space memory, continuous operation test and labyrinth test, were statistically significant (P0.01), but the difference between the scores of the other cognitive tests was poor. There was no significant statistical significance in the opposite sex (P0.05). The results of the biphasic disorder I and the control group showed that all the scores of the cognitive tests were statistically significant (P0.05), while the scores of the four cognitive domains, such as the speed of information processing, the learning of words, the working memory and the social cognition, were statistically significant in the biphasic disorder type II patients and the control group (the control group). P0.05), in visual learning, attention / alertness, reasoning / problem solving, and cognitive test total score, there is no statistically significant difference in.HTR3A and HTR3B gene polymorphism and cognitive function in patients with bipolar disorder. The results show that most of the individuals with HTR3A polymorphic sites with mutation genes are tested for cognitive function test. The scores of the two cognitive domains of the information processing speed and attention / alertness were significantly lower than those of the wild genotypes (p0..05).HTR3A rs1176722, rs2276302 and rs1182457, which were significantly lower than those of the wild homozygous genotypes (P0.05). While most of the individuals with HTR3B polymorphic loci carrying mutation genes were relatively slightly higher in cognitive function tests, especially in the four cognitive domains, such as information processing speed, working memory, attention / alertness, and social cognition, and the cognitive function of the homozygous wild genotypes was relatively impaired (P0.05), except for rs10789970. Outside the three polymorphic loci of rs2276305 and rsl672717, the other HTR3B marker polymorphic loci that carry the mutant genes are significantly less than those of the wild homozygous genotypes (P0.05). Conclusion: 1.HTR3A's rs1176722, rs1176719, rs10160548, rs1176713 and HTR3B rs1176746 mutants Mutations in the mutant genotype that increase the risk of rs1062613 of.HTR3A in patients with bipolar disorder may have the pathogenicity of CCGAG, which is composed of five sites of HTR3A, and CCGAA in patients with bipolar type I may have a linkage inheritance. There may be a linkage genetic.3.HTR3 of the eight loci of HTR3B in patients with bipolar disorder. A individual loci and HTR3B polymorphisms may be associated with the occurrence of psychosis in patients with bipolar disorder that may be related to the polymorphism of the individual loci of the.HTR3A and HTR3B in the patients with bipolar disorder and the majority of the mutation genes of the.HTR3A in the early onset of the bipolar disorder may be associated with the prolongation of the disease course of the bipolar disorder patient with the multiple point mutation of the.HTR3B. The distribution may increase the risk of family heredity,.HTR3A or HTR3B gene polymorphism is not closely related to the frequency of bipolar disorder. The cognitive function of cognitive function in patients with.4. bipolar disorder is generally decreased. The cognitive function of patients with bipolar disorder I in the field of information processing, word learning, working memory and social cognition .HTR3B may have protective effects on cognitive impairment in patients with bipolar disorder, which may have protective effects on cognitive impairment in bipolar disorder patients. Cognitive impairment in the fields of working memory, attention / alertness and social cognition may be the phenotypic characteristics of the patients with bipolar disorder, which may be associated with cognitive impairment in patients with bipolar disorder.
【学位授予单位】：山东大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R749.4
本文编号：2131669
[Abstract]:Objective: to detect the allelic and genotype distribution of 21 labeled single nucleotide polymorphisms (tag SNP) of HTR3A and HTR3B in patients and controls, to explore the genetic susceptibility of bipolar disorder by case control association study and to search for the susceptibility genes of bipolar disorder, and to explore the polymorphism of HTR3A and HTR3BTag SNP genes, genetic imbalances and haplotypes and haplotypes. The relationship between the characteristics of disease and cognitive function in patients with bipolar disorder, further verifying whether cognitive impairment is an internal phenotype of bipolar disorder, provides an important reference for theoretical research and clinical practice, and provides a theoretical basis for the early recognition of bipolar disorder. Methods: the subjects of the case group were from May -2015 June 2013. 209 patients with bipolar disorder hospitalized in Shandong mental health center included 107 patients with bipolar type I and 102 biphasic type II patients. 200 healthy controls were recruited at the same time in the healthy control group. 5m1EDTA anticoagulant was collected, and QIAamp whole blood DNA kit was used to extract genomic DNA. via MALDI-TOF Sequenom MassArray level. The PLINK1.07 and SPSS20.0 statistical software were used to carry out the chi square test and regression analysis, and the SNP and the OR value and the p value were calculated. The OR value and the p value were calculated. The linkage disequilibrium was calculated by Haploview4.2 and the HTR3A and HTR3B single times were constructed to verify the HTR3A, HTR3B polymorphic loci and China. The correlation of the susceptibility to bipolar disorder in the Han nationality. For patients with bipolar disorder, the data included family history, age of onset, frequency of onset and symptoms of psychosis. The case group and healthy control group completed the cognitive function test (including connection test, symbol coding, speech flow) within 1 weeks. Unobstructed, verbal learning, visual spatial memory, maze test, Stroop Color Word Test and continuous operation test, and the correlation between the cognitive impairment of HTR3A and HTR3B Tag SNP and bipolar disorder. Results: the 1. gene frequency and genotype frequency results showed the T allele of the HTR3A site rs1062613, rs1176722 A allele, rs117 6719 A allele, rs10160548 G allele and rs1176713 C allele rs1176746 T allele between the case group and the control group were statistically significant (P0.05).HTR3A and HTR3B marker polymorphic loci in the case group and the control group, the results showed that HTR3A's 176722 The number of individual cases of rs1176719, rs10160548 and rs1176713 loci and HTR3B loci rs1176746 carrying mutant genotype was significantly higher than that of wild homozygous genotype, and the difference was statistically significant (P005).2. haplotype analysis showed that 16 sites of HTR3A and HTR3B were successfully constructed with 3 single links associated with the susceptibility to bipolar disorder. Ploidy, the association of HTR3B's haplotype rs4938056:T, rs12421126:T, rs1176746:C, rs1176744:G, rs2276305:G, rs3782025:T, rs1672717:T, and rs12795805:C was significant (P0.05). The stratified analysis showed that the biphasic disorder type I also constructed 3 haploidy, and the RS10 was 5 polymorphic loci of HTR3A. 62613, rs11604247, rs1176722, rs2276302 and rs1176719 composed of CCGAG, CCGAA, the frequency of the 2 haplotype genes was statistically significant (P005) between the two phase disorder type I and the control group (P005), and the biphasic barrier type II type had 4 haplotypes. The different haplotypes were not statistically significant (P0.05) the clinical characteristics of.3. biphasic disorder and HTR3. The correlation analysis between A and HTR3B markers showed that HTR3A rs11604247, rs2276302, rs10160548, the proportion of psychosis in rs1182457 carrying mutant genes increased significantly (P0.05) than those in the wild homozygous individuals (P0.05), and the proportion of psychotic symptoms in the individuals carrying HTR3A rs1062613 mutant genes was more wild than those in the wild. The patients with homozygous homozygous individuals decreased significantly (P0.05), and the nine loci other than rsl672717 and rs12795805 were significantly associated with bipolar disorder, and the proportion of individuals with rs10789970, rs3831455, rs4938056, rsl2421126, rs1176746 and rs3782025 in the six loci were more than the wild. Patients with homozygous individuals increased significantly (P0.05), the proportion of rs3758987, rs1176744 and rs2276305 mutant genes was significantly lower than those of the wild homozygous individuals (P0.05).HTR3A sites rs10160548, rs1176713 and HTR3B loci rs4938056, rs3782025, and rs1672717 carrying mutant genes. The age of the onset was earlier than the average age of the wild homozygous genotypic group (P0.05). The average onset age of the genotype group carrying the mutant gene in the HTR3B site rs1176746 was later than the average age of the wild homozygous genotype group, and the difference was significant (P0.05).HTR3A most polymorphic loci carrying the mutation gene. The average course of the homozygous wild genotypic group was long in the average course of the type group, and the difference between the two sites of rs1062613 and rs10789980 was statistically significant (P0.05), and the average course of the eight loci, except three loci (rs1176744, rs2276305 and rs12795805), was more than that of the homozygous group. The average course of the wild genotyping group was short, of which the three loci of rs10789970, rs12421126 and rs2276305 were statistically significant between the two groups (P0.05) the.HTR3A site rs10789980 was positively correlated with the number of episodes (r=0.283, P0.01) rs1062613 and family history (r=0.298, P0.01), the rest of the HTR3A sites and family history The site rs4938056 and rs1176744 had no significant correlation with the bipolar disorder family, and the correlation coefficient of rs12795805 and family history (r=0.243, P005) was slightly lower, and the other eight polymorphic loci were significantly correlated with family history (r= 0.262-0.424, P0.01).HTR3B (r= 0.262-0.424, P0.01).HTR3B, only rs227630. 5 a significant correlation with the frequency of seizures (r=0.370, P0.01).4. bipolar disorder case group and the control group compared with the control group, the results of cognitive function showed that the two phase obstacle type I, the two phase obstacle II and the control group three groups in the cognitive test total score and the difference of the cognitive test T scores were statistically significant (F=4.525-8.539, P0.05) biphasic disorder I type and The scores of each cognitive test of bipolar disorder type II were significantly lower than those of the control group. The scores of three cognitive tests, except visual space memory, continuous operation test and labyrinth test, were statistically significant (P0.01), but the difference between the scores of the other cognitive tests was poor. There was no significant statistical significance in the opposite sex (P0.05). The results of the biphasic disorder I and the control group showed that all the scores of the cognitive tests were statistically significant (P0.05), while the scores of the four cognitive domains, such as the speed of information processing, the learning of words, the working memory and the social cognition, were statistically significant in the biphasic disorder type II patients and the control group (the control group). P0.05), in visual learning, attention / alertness, reasoning / problem solving, and cognitive test total score, there is no statistically significant difference in.HTR3A and HTR3B gene polymorphism and cognitive function in patients with bipolar disorder. The results show that most of the individuals with HTR3A polymorphic sites with mutation genes are tested for cognitive function test. The scores of the two cognitive domains of the information processing speed and attention / alertness were significantly lower than those of the wild genotypes (p0..05).HTR3A rs1176722, rs2276302 and rs1182457, which were significantly lower than those of the wild homozygous genotypes (P0.05). While most of the individuals with HTR3B polymorphic loci carrying mutation genes were relatively slightly higher in cognitive function tests, especially in the four cognitive domains, such as information processing speed, working memory, attention / alertness, and social cognition, and the cognitive function of the homozygous wild genotypes was relatively impaired (P0.05), except for rs10789970. Outside the three polymorphic loci of rs2276305 and rsl672717, the other HTR3B marker polymorphic loci that carry the mutant genes are significantly less than those of the wild homozygous genotypes (P0.05). Conclusion: 1.HTR3A's rs1176722, rs1176719, rs10160548, rs1176713 and HTR3B rs1176746 mutants Mutations in the mutant genotype that increase the risk of rs1062613 of.HTR3A in patients with bipolar disorder may have the pathogenicity of CCGAG, which is composed of five sites of HTR3A, and CCGAA in patients with bipolar type I may have a linkage inheritance. There may be a linkage genetic.3.HTR3 of the eight loci of HTR3B in patients with bipolar disorder. A individual loci and HTR3B polymorphisms may be associated with the occurrence of psychosis in patients with bipolar disorder that may be related to the polymorphism of the individual loci of the.HTR3A and HTR3B in the patients with bipolar disorder and the majority of the mutation genes of the.HTR3A in the early onset of the bipolar disorder may be associated with the prolongation of the disease course of the bipolar disorder patient with the multiple point mutation of the.HTR3B. The distribution may increase the risk of family heredity,.HTR3A or HTR3B gene polymorphism is not closely related to the frequency of bipolar disorder. The cognitive function of cognitive function in patients with.4. bipolar disorder is generally decreased. The cognitive function of patients with bipolar disorder I in the field of information processing, word learning, working memory and social cognition .HTR3B may have protective effects on cognitive impairment in patients with bipolar disorder, which may have protective effects on cognitive impairment in bipolar disorder patients. Cognitive impairment in the fields of working memory, attention / alertness and social cognition may be the phenotypic characteristics of the patients with bipolar disorder, which may be associated with cognitive impairment in patients with bipolar disorder.
【学位授予单位】：山东大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R749.4
【参考文献】
相关期刊论文 前3条
1 Daihui Peng;Ting Shen;Linda Byrne;Chen Zhang;Yueqi Huang;Xin Yu;Jingping Zhao;Marita McCabe;David Mellor;Yiru Fang;;Atypical features and treatment choices in bipolar disorders:a result of the National Bipolar Mania Pathway Survey in China[J];Neuroscience Bulletin;2015年01期
2 李志营;于欣;马燕桃;党卫民;;运用德尔菲法对双极性指数评估表适用性的调查[J];中国神经精神疾病杂志;2014年02期
3 CHAN Raymond C K;;Consortium for the Human Information and Neurocognitive Endophenotype (CHINE) in mainland China: An example from neurological soft signs for neuropsychiatric disorders[J];Chinese Science Bulletin;2011年32期
，本文编号：2131669
本文链接：https://www.wllwen.com/yixuelunwen/jsb/2131669.html
最近更新
教材专著
