色氨酸羥化酶基因T3792A位點(diǎn)遺傳多態(tài)性與抑郁癥相關(guān)性及法醫(yī)學(xué)意義
發(fā)布時(shí)間：2018-11-19 22:28
【摘要】： 前言 5-羥色胺(5-hydroxytryptamine,5-HT)是人體新陳代謝過(guò)程中的一個(gè)重要物質(zhì),它廣泛分布于體內(nèi)各組織。作為中樞神經(jīng)遞質(zhì),參與多種神經(jīng)活動(dòng)。5-HT在血液中的濃度,還有它的生理代謝過(guò)程以及在代謝過(guò)程中所涉及的酶類、受體、載體等因素都會(huì)影響5-HT在中樞神經(jīng)系統(tǒng)的正常表達(dá)。 色氨酸羥化酶(tryptophan hydroxylase,TPH)是5-HT合成過(guò)程中的限速酶,它主要分布于大腦和腸嗜鉻細(xì)胞。TPH的生理活性和表達(dá)水平的正常與否影響著5-HT的血濃度,通過(guò)增強(qiáng)或減弱5-TH及其代謝物的作用強(qiáng)度,進(jìn)而影響它在中樞神經(jīng)系統(tǒng)的功能。5-HT的合成和代謝途徑如下:色氨酸→5-羥色胺酸→5-HT→5-羥色醛→5-羥吲哚乙酸(AAAD)。 TPH基因位于染色體11p15.3-p14,在標(biāo)記物D11S151和D11S134之間,全長(zhǎng)29kbp,有13個(gè)外顯子,包括外顯子1(1A,1B,1C),2-1l,共編碼444個(gè)氨基酸。 TPH基因存在多個(gè)變異點(diǎn)且具有遺傳多態(tài)性,這些多態(tài)性位點(diǎn)分別位于上游啟動(dòng)區(qū),內(nèi)含子1B區(qū)、1C區(qū)、內(nèi)含子7、內(nèi)含子8及內(nèi)含子9區(qū),而且在下游3'區(qū)亦有一微衛(wèi)星重復(fù)序列。 本研究選擇TPH基因T3792A位點(diǎn),調(diào)查其在中國(guó)北方漢族群體、藏族群體及抑郁癥患者群體中的遺傳多態(tài)性,并探討TPH基因T3792A位點(diǎn)的遺傳多態(tài)性與抑郁癥的關(guān)聯(lián)性及其法醫(yī)學(xué)意義。 材料和方法 根據(jù)目標(biāo)序列設(shè)計(jì)引物,應(yīng)用ASPCR技術(shù)擴(kuò)增TPH基因T3792A,以聚丙烯酰胺凝膠電泳分離結(jié)合銀染顯帶的方法,對(duì)302例中國(guó)北方漢族個(gè)體、135例中國(guó)藏族個(gè)體及113例抑郁癥患者進(jìn)行了基因分型。 結(jié)果 302例中國(guó)北方漢族個(gè)體血液樣品,通過(guò)常規(guī)電泳法檢測(cè)其基因型,檢出AA型78例,AT型169例,TT型55例。計(jì)算得出等位基因A頻率為0.538,等位基因T頻率為0.462。113例抑郁癥患者血液樣品經(jīng)過(guò)檢測(cè),檢出AA型44例,AT型52例,TT型17例。計(jì)算得出等位基因A頻率為0.619,等位基因T頻率為0.381。135例中國(guó)藏族個(gè)體血液樣品,經(jīng)過(guò)檢測(cè)檢出AA型22例,AT型69例,TT型44例。計(jì)算得出等位基因A頻率為0.419,等位基因T頻率為0.581。 討論 通過(guò)對(duì)302例中國(guó)北方漢族個(gè)體、135例中國(guó)藏族個(gè)體TPH基因T3792A位點(diǎn)遺傳多態(tài)性分析,所得數(shù)據(jù)基因型分布符合Hardy-Weinberg平衡定律。根據(jù)對(duì)TPH基因T3792A位點(diǎn)在中國(guó)北方漢族群體、中國(guó)藏族群體中的等位基因頻率和基因型頻率分別計(jì)算得出:TPH基因T3792A位點(diǎn)在中國(guó)北方漢族群體的DP值為0.587,H值為0.497,EPP值為0.187。在中國(guó)藏族群體中的DP值為0.606,H值為0.487,EPP值為0.184。表明該位點(diǎn)在兩個(gè)群體中屬于高鑒別能力的遺傳標(biāo)記系統(tǒng),適合法醫(yī)學(xué)的應(yīng)用。 本實(shí)驗(yàn)的研究結(jié)果表明,TPH基因T3792A位點(diǎn)在抑郁癥患者群體和健康對(duì)照群體中,基因型頻率分布組間比較存在顯著性差異,具有統(tǒng)計(jì)學(xué)意義(x~2=4.422,P=0.035)。同時(shí),在抑郁癥患者群體中等位基因A的頻率明顯高于健康對(duì)照群體的頻率。抑郁癥患者群體中的AA基因型頻率也高于健康對(duì)照群體的頻率。因此推測(cè)TPH基因T3792A位點(diǎn)等位基因A與抑郁癥之間有一定的關(guān)聯(lián)性,可能是抑郁癥的易感等位基因。 將本文獲得的數(shù)據(jù)與文獻(xiàn)中報(bào)道的法國(guó)白種人群體的等位基因頻率(A=0.660,T=0.340)進(jìn)行比較,漢族與藏族、漢族與法國(guó)白人及藏族與法國(guó)白人之間均表現(xiàn)為顯著性差異(P＜0.01),提示TPH基因T3792A位點(diǎn)的遺傳多態(tài)性可能具有種族、民族或地域差異,是人類遺傳學(xué)研究的重要遺傳標(biāo)記。 結(jié)論 1、TPH基因T3792A位點(diǎn)在中國(guó)北方漢族群體、藏族群體中具有較好的多態(tài)性分布,是法醫(yī)學(xué)個(gè)人識(shí)別和親子鑒定中可應(yīng)用的重要遺傳標(biāo)記。 2、中國(guó)漢族群體中TPH基因T3792A位點(diǎn)的T-A突變可能與抑郁癥具有關(guān)聯(lián)性。 3、TPH基因T3792A位點(diǎn)的遺傳多態(tài)性具有民族、種族差別。
[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.
【學(xué)位授予單位】：中國(guó)醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2008
【分類號(hào)】：R749.4;d919
本文編號(hào)：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.
【學(xué)位授予單位】：中國(guó)醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2008
【分類號(hào)】：R749.4;d919
【引證文獻(xiàn)】
相關(guān)期刊論文 前1條
1 趙宗峰;張艷君;王慧琴;依布拉音;;新疆維吾爾族群體色氨酸羥化酶1基因T3804A位點(diǎn)多態(tài)性與抑郁癥的關(guān)聯(lián)[J];中國(guó)健康心理學(xué)雜志;2013年08期
，本文編號(hào)：2343631
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