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	中国西北地区汉族人群5-羟色胺2A受体启动区和色氨酸羟化酶2基因多态性与心境障碍及帕罗西汀药物疗效相关性分析
Alternative Title	Association Study of 5-HTR2A Promoter Region and TPH 2 Gene Polymorphisms with Affective Disorder and Paroxetine Treatment Response in Northwest Chinese Han People
	柳文华
Thesis Advisor	张兰 ; 殷宏
	2011-05-13
Degree Grantor	兰州大学
Place of Conferral	兰州
Degree Name	硕士
Keyword	心境障碍 5-羟色胺2A受体 色氨酸羟化酶2 基因多态性 盐酸帕罗西汀
Abstract	第一部分 5-羟色胺2A受体(-1438A/G)启动区基因多态性与心境障碍相关性研究 目的：探讨中国西北地区汉族人群5-羟色胺2A受体(-1438A/G)启动区[5-HTR2A(-1438A/G)]基因多态性与心境障碍的发病、性别、自杀相关是否相关。 方法：应用聚合酶链反应（PCR）扩增技术及测序方法测定160例心境障碍患者和160例正常对照的5-HTR2A基因型和等位基因，分别验证各种基因型及等位基因频率与发病、性别、自杀相关的相关性。 结果：5-HTR2A(-1438A/G)：①共检出3种片段：513bp、331bp和182bp，对应3种基因型：AA、AG、AA型。②病例组与对照组比较基因型分布频率(χ2=6.503, P=0.039)及等位基因频率(χ2=4.025, P=0.045)差异均有统计学意义，病例组A/G、G/G基因型和G等位基因频数均高于对照组(47.5% vs. 40.6%;38.7% vs. 34.4%；62.5% vs. 54.7%)；两组性别分层比较，女性基因型(χ2=8.485, P=0.014)及等位基因频率(χ2=8.649, P=0.003)差异有统计学意义，患者GG基因型与G等位基因频率均高于对照组(40.9% vs.21.9; 63.3% vs. 47.3%),而男性病例组与对照组比较，差异无统计学意义（P﹥0.05）；病例组亚型分层比较，双相情感障碍(抑郁相)组与正常对照组比较基因型频率( χ2=0.012, P =0.994)及等位基因频率 ( χ2=0.005, P =0.946)差异均无统计学意义，单相抑郁症组与正常对照组比较基因型(χ2=8.412, P =0.015)及等位基因频率(χ2=5.236, P=0.022)差异有统计学意义，病例组A/G、G/G基因型和G等位基因频数均高于对照组（48.5% vs.40.6;39.7% vs. 34.4%;64.0% vs.54.7%）；单相抑郁症与双相障碍-抑郁相两组间进行比较差异无统计学意义(P﹥0.05)；病例组有无自杀相关分层比较基因型频率(χ2=0.060, P=0.970)及等位基因频率(χ2=0.038, P=0.845)差异均无统计学意义(P﹥0.05)；自杀相关性别分层比较基因型频率(χ2=1.384, P=0.501)与等位基因频率差异均无统计学意义(χ2=0.016, P=0.898)。 结论：中国西北地区汉族人群5-HTR2A(-1438A/G)启动区多态性与心境障碍的发病相关，尤其与单项抑郁症相关。A/G、G/G基因型可能是心境障碍的易感基因型，G等位基因可能是心境障碍的易感基因。且G基因可能是女性罹患心境障碍的危险因子。 第二部分5-HTR2A(-1438A/G)启动区基因多态性与盐酸帕罗西汀治疗相关性分析 目的：探讨5-HTR2A(-1438A/G)启动区基因多态性与SSRIs类药物盐酸帕罗西汀疗效是否关联。 方法：在分析多态性的基础上，对136例单相抑郁症患者和24例双相障碍抑郁相进行为期4周的盐酸帕罗西汀药物治疗试验，HMAD量表检测疗效。 结果：单相抑郁症患者5-HTR2A(-1438A/G)启动区多态性含A等位基因组与不含该等位基因组组间疗效差异有统计学意义(F=6.317，P=0.013)，主要体现在第2周末(χ2=5.878，P=0.015),AA组、AG组有效率均高于GG组，且AA组高于AG组(分别为87.8%，57.6%，53.7%)。在双相情感障碍患者中，基因型的差异对盐酸帕罗西汀药物疗效影响无统计学意义(F=0.702, P =0.507)。 结论：1.在单相抑郁症患者中，5-HTR2A(-1438A/G)启动区多态性和SSRIs类抗抑郁药物盐酸帕罗西汀疗效相关，尤其具有A等位基因纯合子的...
Other Abstract	PartⅠ Association Study of 5-HTR2A(-1438A/G) Promoter Region gene polymorphisms and Affective Disorder Object To explore the association between the 5-HTR2A（-1438A/G）promoter region gene polymorphisms and episode, gender, suicidality and subtypes of affective disorder in Chinese Han people . Methods Polymerase chain reaction (PCR) was used to detect the distributive frequency of serotonin 2A receptor promoter region polymorphisms of 160 affective disorder patients(patient group) and 160 normal people (control group) as well as PCR and sequencing skills were applied to detect the association between serotonin 2A receptor gene polymorphisms with episode, gender, suicidality and subtypes of affective disorder of 160 affective disorder patients and 160 normal people. Results 5-HTR2A(-1438A/G):①There were AA, AG, GG genotypes according to the two alleles of 513bp,331bp和182bp.②There were significant differences of the 5-HTR2A genotypes(χ2=6.503, P=0.039) and the alleles（χ2=4.025, P=0.045）between the patient group and the control group. The frequency of GG (38.7% vs. 34.4%),AG(47.5% vs. 40.6%) genotypes;and G allele (62.5% vs. 54.7%) in patients was higher than that in control group. Significant difference of allele frequency could be found (χ2=8.649, P=0.003) between women patients group and the control group.GG genotypes (40.9% vs.21.9%) and G allele (63.3% vs.47.3%) in women patients was higher than those in control group.But there was no significant difference between man patients and control group (p﹥0.05). There was no significant difference between Bipolar disorder(depressive phase)( χ2=0.012,p=0.994; χ2=0.005,p=0.946)with control group. Significant differences of genotypes(χ2=8.412,p=0.015) and allele(χ2=5.236,p=0.022) frequency could be found between the Unipolar depression patients and the control group. The insignificant differences could be found between the affective disorder patients with and without suicidality behavior either for the frequency of the genotypes(χ2=0.060,P=0.970) or that of the alleles(χ2=0.038,P=0.845). There was no significant difference about the distributive frequency of genotypes(χ2=1.384,P=0.501) and alleles(χ2=0.016,P=0.898) of 5-HTR2A between the different gender affective disorder patients with suicidality behavior. Conclusions 5-HTR2A(-1438A/G): 5-HTR2A gene polymorphism related to the episode of affective disorder in northwest Chinese Han people,especially to the Unipolar depression. AG or G...
URL	查看原文
Language	中文
Document Type	学位论文
Identifier	https://ir.lzu.edu.cn/handle/262010/222212
Collection	学院待认领
Affiliation	临床医学院
Recommended Citation GB/T 7714	柳文华. 中国西北地区汉族人群5-羟色胺2A受体启动区和色氨酸羟化酶2基因多态性与心境障碍及帕罗西汀药物疗效相关性分析[D]. 兰州. 兰州大学,2011.

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