色氨酸羟化酶基因T3792A位点遗传多态性与抑郁症相关性及法医学意义
发布时间：2018-11-19 22:28
【摘要】： 前言 5-羟色胺(5-hydroxytryptamine,5-HT)是人体新陈代谢过程中的一个重要物质,它广泛分布于体内各组织。作为中枢神经递质,参与多种神经活动。5-HT在血液中的浓度,还有它的生理代谢过程以及在代谢过程中所涉及的酶类、受体、载体等因素都会影响5-HT在中枢神经系统的正常表达。 色氨酸羟化酶(tryptophan hydroxylase,TPH)是5-HT合成过程中的限速酶,它主要分布于大脑和肠嗜铬细胞。TPH的生理活性和表达水平的正常与否影响着5-HT的血浓度,通过增强或减弱5-TH及其代谢物的作用强度,进而影响它在中枢神经系统的功能。5-HT的合成和代谢途径如下:色氨酸→5-羟色胺酸→5-HT→5-羟色醛→5-羟吲哚乙酸(AAAD)。 TPH基因位于染色体11p15.3-p14,在标记物D11S151和D11S134之间,全长29kbp,有13个外显子,包括外显子1(1A,1B,1C),2-1l,共编码444个氨基酸。 TPH基因存在多个变异点且具有遗传多态性,这些多态性位点分别位于上游启动区,内含子1B区、1C区、内含子7、内含子8及内含子9区,而且在下游3'区亦有一微卫星重复序列。 本研究选择TPH基因T3792A位点,调查其在中国北方汉族群体、藏族群体及抑郁症患者群体中的遗传多态性,并探讨TPH基因T3792A位点的遗传多态性与抑郁症的关联性及其法医学意义。 材料和方法 根据目标序列设计引物,应用ASPCR技术扩增TPH基因T3792A,以聚丙烯酰胺凝胶电泳分离结合银染显带的方法,对302例中国北方汉族个体、135例中国藏族个体及113例抑郁症患者进行了基因分型。 结果 302例中国北方汉族个体血液样品,通过常规电泳法检测其基因型,检出AA型78例,AT型169例,TT型55例。计算得出等位基因A频率为0.538,等位基因T频率为0.462。113例抑郁症患者血液样品经过检测,检出AA型44例,AT型52例,TT型17例。计算得出等位基因A频率为0.619,等位基因T频率为0.381。135例中国藏族个体血液样品,经过检测检出AA型22例,AT型69例,TT型44例。计算得出等位基因A频率为0.419,等位基因T频率为0.581。 讨论 通过对302例中国北方汉族个体、135例中国藏族个体TPH基因T3792A位点遗传多态性分析,所得数据基因型分布符合Hardy-Weinberg平衡定律。根据对TPH基因T3792A位点在中国北方汉族群体、中国藏族群体中的等位基因频率和基因型频率分别计算得出:TPH基因T3792A位点在中国北方汉族群体的DP值为0.587,H值为0.497,EPP值为0.187。在中国藏族群体中的DP值为0.606,H值为0.487,EPP值为0.184。表明该位点在两个群体中属于高鉴别能力的遗传标记系统,适合法医学的应用。 本实验的研究结果表明,TPH基因T3792A位点在抑郁症患者群体和健康对照群体中,基因型频率分布组间比较存在显著性差异,具有统计学意义(x~2=4.422,P=0.035)。同时,在抑郁症患者群体中等位基因A的频率明显高于健康对照群体的频率。抑郁症患者群体中的AA基因型频率也高于健康对照群体的频率。因此推测TPH基因T3792A位点等位基因A与抑郁症之间有一定的关联性,可能是抑郁症的易感等位基因。 将本文获得的数据与文献中报道的法国白种人群体的等位基因频率(A=0.660,T=0.340)进行比较,汉族与藏族、汉族与法国白人及藏族与法国白人之间均表现为显著性差异(P＜0.01),提示TPH基因T3792A位点的遗传多态性可能具有种族、民族或地域差异,是人类遗传学研究的重要遗传标记。 结论 1、TPH基因T3792A位点在中国北方汉族群体、藏族群体中具有较好的多态性分布,是法医学个人识别和亲子鉴定中可应用的重要遗传标记。 2、中国汉族群体中TPH基因T3792A位点的T-A突变可能与抑郁症具有关联性。 3、TPH基因T3792A位点的遗传多态性具有民族、种族差别。
[Abstract]:Foreword 5-hydroxytryptamine (5-HT) is an important substance in the process of human metabolism, and it is widely distributed in the body The concentration of 5-HT in the blood and its physiological and metabolic processes, as well as the enzymes, receptors, carriers involved in the metabolism, will affect the positive and negative effects of 5-HT in the central nervous system. Tryptophan hydroxylase (TPH) is a speed-limiting enzyme in the synthesis of 5-HT. The physiological activity and expression level of TPH affect the blood concentration of 5-HT. By enhancing or decreasing the effect of 5-TH and its metabolites, it affects the function of the 5-HT in the central nervous system. and the metabolic pathway is as follows: tryptophan, 5-hydroxytryptamine, 5-hydroxytryptamine, 5-hydroxytryptamine, 5-hydroxytryptamine, Acid (AAAD). The TPH gene is located in chromosome 11p15.3-p14, between the markers D11S151 and D11S134, with a total length of 29kbp, with 13 exons, including exon 1 (1A, 1B, 1C), 2-1l the TPH gene has a plurality of mutation points and has genetic polymorphism, and the polymorphic sites are respectively located in the upstream starting region, the intron 1B region, the 1C region, the intron 7, the intron 8 and the intron 9 region, The T3792A site of TPH gene was selected to investigate the genetic polymorphism of TPH gene T3792A. the transmission of polymorphism The invention relates to the association of depression and the forensic significance. The material and the method design a primer according to a target sequence, 13 Genotyping was carried out in 5 Chinese Tibetan individuals and 113 patients with depression. The genotype was detected by conventional electrophoresis, and 78 cases of type A, 169 cases of AT type and 55 cases of TT type were detected. The frequency of allele A was 0.538, and the frequency of allele T was 0.462.113. The blood samples of the patients with depression were detected, A-A 44 cases, AT-type 52 cases and TT-type 17 cases were detected. The frequency of the allele A was 0.619 and the allele T frequency was 0.381. 135 cases were found in China. The blood samples of the Tibetan individuals were detected and detected in 22 cases, type A, 69, TT type. 44 The results showed that the allele A frequency was 0.419 and the allele T frequency was 0.581. The TPH gene T3 of the Chinese Tibetan individuals in China was investigated by the study of 302 Chinese Han individuals and 135 Chinese Tibetan individuals. The genetic polymorphism of the 792A locus is analyzed, and the distribution of the obtained data is in accordance with the Hardy-Weinberg equilibrium law. According to the allele frequency and the genotype frequency of the T3792A site of the TPH gene T3792A in the northern Chinese Han population, the TPH gene T379 The DP of the 2A site in the Han population in the northern part of China was 0. 587, the H value was 0.497, and the EPP value was 0.. 187. The DP value in the Tibetan population in China is 0.606, and the H value is 0.487, and EP The results of this experiment show that the T3792A site of TPH gene is in the group of patients with depression and the healthy control group. There was a significant difference between the genotype frequency distribution groups and the statistical significance (x ~ 2 = 4).. 422, P = 0. 035). At the same time, in the middle of the group of patients with depression The frequency of the A is significantly higher than the frequency of the healthy control population. The frequency of the AA genotype in the depression patient population is also higher than the frequency of the healthy control population. It is suggested that there is a certain association between the allele A and the depression in the T3792A locus of the TPH gene, which may be the susceptibility allele of the depression. The data obtained in this paper and the allele frequency of the French Caucasians reported in the literature (A = 0.660, T = (0. 340) The difference between the Han and the Tibetan, the Han and French white and the white and French white people was significant (P <0.01). prompt The genetic polymorphism of the T3792A site in the TPH gene may have a racial, national or regional difference, which is an important genetic marker for human genetic studies. Because the T3792A site has a better polymorphism distribution in the Han population in the northern part of China and the Tibetan population, it is a forensic medicine. an important genetic marker that can be used in human identification and paternity test.
【学位授予单位】：中国医科大学
【学位级别】：硕士
【学位授予年份】：2008
【分类号】：R749.4;d919
本文编号：2343631
[Abstract]:Foreword 5-hydroxytryptamine (5-HT) is an important substance in the process of human metabolism, and it is widely distributed in the body The concentration of 5-HT in the blood and its physiological and metabolic processes, as well as the enzymes, receptors, carriers involved in the metabolism, will affect the positive and negative effects of 5-HT in the central nervous system. Tryptophan hydroxylase (TPH) is a speed-limiting enzyme in the synthesis of 5-HT. The physiological activity and expression level of TPH affect the blood concentration of 5-HT. By enhancing or decreasing the effect of 5-TH and its metabolites, it affects the function of the 5-HT in the central nervous system. and the metabolic pathway is as follows: tryptophan, 5-hydroxytryptamine, 5-hydroxytryptamine, 5-hydroxytryptamine, 5-hydroxytryptamine, Acid (AAAD). The TPH gene is located in chromosome 11p15.3-p14, between the markers D11S151 and D11S134, with a total length of 29kbp, with 13 exons, including exon 1 (1A, 1B, 1C), 2-1l the TPH gene has a plurality of mutation points and has genetic polymorphism, and the polymorphic sites are respectively located in the upstream starting region, the intron 1B region, the 1C region, the intron 7, the intron 8 and the intron 9 region, The T3792A site of TPH gene was selected to investigate the genetic polymorphism of TPH gene T3792A. the transmission of polymorphism The invention relates to the association of depression and the forensic significance. The material and the method design a primer according to a target sequence, 13 Genotyping was carried out in 5 Chinese Tibetan individuals and 113 patients with depression. The genotype was detected by conventional electrophoresis, and 78 cases of type A, 169 cases of AT type and 55 cases of TT type were detected. The frequency of allele A was 0.538, and the frequency of allele T was 0.462.113. The blood samples of the patients with depression were detected, A-A 44 cases, AT-type 52 cases and TT-type 17 cases were detected. The frequency of the allele A was 0.619 and the allele T frequency was 0.381. 135 cases were found in China. The blood samples of the Tibetan individuals were detected and detected in 22 cases, type A, 69, TT type. 44 The results showed that the allele A frequency was 0.419 and the allele T frequency was 0.581. The TPH gene T3 of the Chinese Tibetan individuals in China was investigated by the study of 302 Chinese Han individuals and 135 Chinese Tibetan individuals. The genetic polymorphism of the 792A locus is analyzed, and the distribution of the obtained data is in accordance with the Hardy-Weinberg equilibrium law. According to the allele frequency and the genotype frequency of the T3792A site of the TPH gene T3792A in the northern Chinese Han population, the TPH gene T379 The DP of the 2A site in the Han population in the northern part of China was 0. 587, the H value was 0.497, and the EPP value was 0.. 187. The DP value in the Tibetan population in China is 0.606, and the H value is 0.487, and EP The results of this experiment show that the T3792A site of TPH gene is in the group of patients with depression and the healthy control group. There was a significant difference between the genotype frequency distribution groups and the statistical significance (x ~ 2 = 4).. 422, P = 0. 035). At the same time, in the middle of the group of patients with depression The frequency of the A is significantly higher than the frequency of the healthy control population. The frequency of the AA genotype in the depression patient population is also higher than the frequency of the healthy control population. It is suggested that there is a certain association between the allele A and the depression in the T3792A locus of the TPH gene, which may be the susceptibility allele of the depression. The data obtained in this paper and the allele frequency of the French Caucasians reported in the literature (A = 0.660, T = (0. 340) The difference between the Han and the Tibetan, the Han and French white and the white and French white people was significant (P <0.01). prompt The genetic polymorphism of the T3792A site in the TPH gene may have a racial, national or regional difference, which is an important genetic marker for human genetic studies. Because the T3792A site has a better polymorphism distribution in the Han population in the northern part of China and the Tibetan population, it is a forensic medicine. an important genetic marker that can be used in human identification and paternity test.
【学位授予单位】：中国医科大学
【学位级别】：硕士
【学位授予年份】：2008
【分类号】：R749.4;d919
【引证文献】
相关期刊论文 前1条
1 赵宗峰;张艳君;王慧琴;依布拉音;;新疆维吾尔族群体色氨酸羟化酶1基因T3804A位点多态性与抑郁症的关联[J];中国健康心理学杂志;2013年08期
，本文编号：2343631
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