偏头痛与5-羟色胺转运体基因多态性的相关性研究

目的研究5-羟色胺转运体(5-hydroxytryptamine transporter,5-HTT)基因多态性频率在汉族偏头痛人群的分布,探讨该基因多态性与偏头痛的相关性。方法采集40例偏头痛患者(实验组)和40例健康成人(对照组)的肘静脉血,通过DNA-PCR扩增等分子生物学技术,观察5-HTT基因多态性的基因型和等位基因频率在两组中的分布特点。结果5-HTT基因多态性的基因型和等位基因频率在实验组和对照组中的分布无统计学差异(P>0.05),在偏头痛各临床特征中的分布也无统计学差异(P>0.05)。结论5-HTT基因是否在汉族人群偏头痛发病中起作用,有待进一步研究。     

5-羟色胺转运体基因多态性与SSRIs疗效

本文就5-羟色胺转运体多态性与SSRIs疗效之间关系作一综述。     

5-羟色胺转运体基因多态性与SSRIs疗效

本文就 5 -羟色胺转运体多态性与 SSRIs疗效之间关系作一综述。     

偏头痛患者5-羟色胺2A受体启动子区T102C基因多态性的研究

目的 探讨5-羟色胺2A受体(5-HT2AR)基因T102C多态性与哈尔滨地区汉族人偏头痛的关系.方法 应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法,检测204例偏头痛患者及186例健康对照者5-HT2AR基因启动子区域T102C多态性.结果 偏头痛患者中T/T,T/C,C/C分布为29.9%,53.9%和16.2%,正常对照中T/T,T/C,C/C分布为35.0%,48.9%和16.1%,两组间无显著性差异(P>0.05).偏头痛患者的等位基因频率为102T 56.9%,102C 43.1%,正常对照组为102T 59.4%,102C 40.6%,两组间无显著性差异(P>0.05).结论 5-HT2AR基因启动子区域T102C基因多态性与哈尔滨地区汉族人偏头痛的发生无相关性.

Abstract：

Objective To investigate the association between 5-HT2A receptor (5-HT2AR) promoter T102C gene polymorphism and migraine in Han nationality, Harbin. Methods Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP)analysis were applied to determine the genotypes at the promoter 102 of 5-HT2AR gene in 204 migraine patients and 186 controls. The genotype distribution and allele frequencies among different groups were compared. Results The genotype T/T,T/C,C/C distribution of the 5-HT2AR were 29.9% ,53.9% and 16.2% in migraine patients,and were 35.0% ,48.9% and 16.1% in controls (P > 0.05). The allele frequencies of 5-HT2AR in migraine patients were 56.9% for 102T,43.1% for 102C,and 59.4% for 102T,40.6% for 102C in controls (P > 0.05 ).Conclusion The polymorphism of 5-HT2AR promoter T102C gene was not significantly associated with migraine among Han nationality,in Harbin, China.     

5-羟色胺转运体基因多态性与精神分裂症的相关性研究

目的：探讨中国汉族人群中5一羟色胺转运体（5-HTT）基因与精神分裂症之间的相关性。方法：189例符合中国精神障碍分类与诊断标准第3版及美国精神障碍诊断与统计手册第4版精神分裂症诊断标准的患者（患者组）使用聚合酶链式反应扩增5-HTT基因的启动子区（5-HTrLPR）位点和内含子区（5-HTTVNTR）位点,以琼脂糖凝胶电泳分离法进行基因分型,并和300名正常人（正常对照组）进行对照。结果：患者组与正常对照组之间5-HTTLPR位点L／L、L／S和S／S基因型频率以及等位基因L、s频率分布上差异具有统计学意义（x2=47．882,x2=44．188;P〈0．01或P〈0．001）;5-HTTVNTR位点12／12、12／10、10／10基因型频率和等位基因10、12频率分布上差异无统计学意义（X2=0．335,X。=0．051;P均〉0．05）。结论：S／S基因型及S等位基因可能是精神分裂症患者的易感等位基因;5-HT．TVNTR位点在中国汉族人群精神分裂症发病机制中可能不起主要作用。     

儿童孤独症与5-羟色胺转运体基因连锁多态性区域的关联性研究

目的:探讨汉族人群中5-羟色胺转运体基因连锁多态性区域(5-HTTLPR)与儿童孤独症(CA)的相关性. 方法:采用病例对照研究、聚合酶链反应(PCR)的方法对中国汉族CA患儿与5-HTTLPR的关联性进行研究.以健康儿童作对照. 结果:中国汉族CA患者的5-HTTLPR分布与对照组差异无显著性,但CA组5-HTTLPR纯合子基因型的频率显著高于对照组;5-HTTLPR的基因型与CA的躯体运动因子显著相关. 结论:5-HTTLPR与CA的主要症状存在显著关联;5-HTTLPR的纯合子基因型和等位基因L可能增加了CA的患病危险.     

广泛性焦虑障碍与5-羟色胺转运体基因多态性的相关研究

目的　探讨广泛性焦虑障碍与 5 羟色胺转运体 (5 HTT)基因启动子区和内含子 2区两种多态性的相关性。方法　运用聚合酶链反应技术检测 4 7例广泛性焦虑障碍患者 (患者组 )和 90名健康对照者 (对照组 )两种基因多态性的分布频率。结果　患者组启动子区多态性 (5 HTTLPR)的short/short(SS)基因型和short(S)等位基因频率分别为 72 %和 83% ,对照组SS基因型和S等位基因频率分别为 4 9%和 71% ,两组间的差异有显著性 (P <0 0 5 )。内含子 2区数目可变的顺向重复多态性各基因型 (12 / 12 ,12 / 10 ,10 / 10 )频率在患者组中分别为 72 % ,2 6 % ,2 % ,在对照组中分别为 78% ,2 1% ,1% ,两组间的差异无显著性 (P >0 0 5 ) ;等位基因频率比较的差异亦无显著性 (P >0 0 5 )。结论　 5 HTTLPR的SS基因型可能是广泛性焦虑障碍的易感基因之一。     

5-HTTLPR多态性与偏头痛的关系的系统评价

目的本研究旨在使用系统评价方法评估5-HT转运体基因多态性(5-HTT gene-linkedpolymorphic region,5-HTTLPR)和偏头痛的关系。方法广泛检索中英文数据库中发现相关研究,对符合纳入标准的每个研究提取等位基因和基因型频率,使用随机或固定效应模型计算比值比(OR),使用Q检验检测研究之间的异质性,Egger’s(埃格)测试和漏斗图评估发表偏倚,对以家庭为基础的关联研究进行描述性分析。结果总共12个研究纳入meta分析,没有发现5-HTTLPR多态性与偏头痛具有相关性。结论证据未表明5-HTTLPR多态性与偏头痛患病风险有关,该结论需大样本研究进一步验证。     

原发性失眠的5-羟色胺转运体基因遗传多态性研究

目的　探讨原发性失眠与羟色胺转运体( 5 -HTT)基因遗传多态性的关系。方法　对85例病例组和54名对照组提取外周血基因组DNA ,进行PCR扩增,分析相应的基因型,并比较两组不同基因型患者的焦虑和抑郁评分有无差异。结果　两组的5 -HTTLPR和5 -HTTVNTR的基因型、等位基因频率及不同基因型频率的两两比较均无显著性差异(P >0 .0 5) ;病例组5- HTTLPR的S/S(S组)和S/L +L/L(L组)两组之间及5- HTTVNTR的1 0 / 1 0 + 1 0 / 1 2 ( 1 0组)和1 2 / 1 2 ( 1 2组)两组之间的焦虑、抑郁量表评分比较均无显著性差异(P >0 . 0 5)。结论　5- HTTLPR和5 -HTTVNTR两种基因遗传多态性与原发性失眠的关系尚需进一步探讨。     

5-羟色胺转运体基因多态性与脑卒中后抑郁的关系

目的 探讨5-羟色胺转运体基因启动子区域多态性(5-HTTLPR)与中国汉族人群脑卒中后抑郁(PSD)的关系.方法 应用PCR技术,比较96例PSD、97例脑卒中后非PSD及60名健康对照组上述位点基因型及等位基因频率.结果 PSD组5-HTTLPR多态的S/S基因型频率和S等位基因频率显著高于脑卒中非PSD组和健康对照组(均P＜0.05),S等位基因与PSD呈正关联(比值比OR=1.76,P＜0.01,95％CI:1.15～2.69).结论 5-HTTLPR S/S基因型和S等位基因可能为脑卒中后抑郁的易患因素.     

Meta-analysis reveals association between serotonin transporter gene STin2 VNTR polymorphism and schizophrenia

The serotonin transporter gene (SLC6A4) is a candidate gene for schizophrenia based on serotonin transporter's crucial role in serotonergic neurotransmission. However, association studies have produced conflicting results regarding the association between two common SLC6A4 gene polymorphisms, the promoter insertion/deletion (5-HTTLPR) and the intron 2 VNTR (STin2 VNTR) polymorphisms, and schizophrenia susceptibility. To further elucidate the putative association between the two SLC6A4 gene polymorphisms and schizophrenia susceptibility, we performed a meta-analysis based on all original published association studies between schizophrenia and the 5-HTTLPR and STin2 VNTR polymorphisms published before April 2004. Our analyses showed no statistically significant evidence for the association between the Short allele of the 5-HTTLPR polymorphism and schizophrenia (random-effects pooled odds ratio (OR)=0.99, 95% Confidence Interval (CI)=0.92-1.07, Z=-0.23, P=0.82) from 19 population-based association studies consisting of 2990 case and 3875 control subjects. However, highly significant evidence for association between the STin2.12 allele of the STin2 VNTR polymorphism (random-effects pooled OR=1.24, 95% CI=1.11-1.38, Z=3.82, P=0.00014) and schizophrenia was found from 12 population-based association studies consisting of 2177 cases and 2369 control subjects. Our meta-analysis suggests that the STin2.12 allele of the STin2 VNTR polymorphism is likely a risk factor for schizophrenia susceptibility. Our data imply that following completion of the International HapMap Project, a comprehensive evaluation of a set of markers that fully characterize the linkage disequilibrium relationships at the SLC6A4 gene should be tested in large well-characterized clinical samples in order to understand the role of this gene in schizophrenia susceptibility.     

Significance of serotonin transporter gene polymorphism in migraine.

OBJECTIVE: To elucidate significance of the serotonin transporter gene (STG) polymorphism in migraine, and to address the polymorphic patterns of STG, both in the migraineurs and healthy people in this country. STUDY DESIGN: A PCR study of STG in 52 migraineurs and 80 healthy controls. METHODS: Using the PCR technique, STG polymorphism was studied in the DNA obtained from leukocytes of the patients and healthy controls. Polymorphism of the two regions (VNTR and 5-HTTLPR) of STG was assessed. RESULTS: VNTR STin 2.10 and STin 2.12 alleles were detected in migraineurs and healthy controls. Both homozygous and heterozygous STin 2.10 allele predominated in the migraine group (p=0.01), while STin 2.12 allele was more frequent in the healthy controls (p=0.02). There was no relationship between the migraine type, family history of migraine and STG polymorphism. CONCLUSION: STin 2.10 and STin 2.12 alleles of VNTR are frequent in this country. While the presence of STin 2.10 allele increases the risk of migraine, 5-HTTLPR polymorphism is not associated with this risk.     

Association of the STin2 polymorphism of the serotonin transporter gene with a neurocognitive endophenotype in major depressive disorder

BACKGROUND:: The aim of our study was to investigate the association of STin2 polymorphism and cognitive dysfunction in major depression. METHODS:: 71 patients with major depression and 99 controls were genotyped for STin2. All depressive subjects and 30 controls also completed tests measuring neurocognitive performance. RESULTS:: We found a significantly higher frequency of the STin2.10/Stin2.10 homozygous genotype in the depressed group compared to controls. In the depressed group subjects with at least one copy of the 10-repeat allele showed decreased interference threshold in Stroop III compared to patients without the 10-repeat allele. Average performance of the depressed group without the 12-repeat allele was significantly weaker in the Rey Auditory Verbal Learning Test working memory and recall tasks compared to patients having at least one copy of the 12-repeat allele. CONCLUSION:: Our results suggest that the presence of STin2.10 and absence of STin2.12 allele may be related to a possible genetic endophenotype for characteristic cognitive dysfunctions detected in MDD.     

A functional serotonin transporter gene polymorphism is associated with migraine with aura

An association study was performed in 197 migraineurs with regard to a functional serotonin (5-HT) transporter (5-HTT) gene promoter polymorphism that leads to low or high 5-HT uptake activity. The frequency of the less active short allele was increased in migraineurs with aura but not in migraineurs without aura in comparison with the control population (p < 0.001). This indicates that the 5-HTT may be involved in the polygenic etiology of migraine with aura.     

Influence of SERTPR and STin2 in the serotonin transporter gene on the effect of selective serotonin reuptake inhibitors in depression: a systematic review

Large differences in clinical response to selective serotonin reuptake inhibitors (SSRIs) are observed in depressive patients with different genotypes. Quantification of these differences is needed to decide if genetic testing prior to antidepressant treatment is useful. We conducted a systematic review of the literature on the influence of polymorphisms in the serotonin transporter gene (SERTPR (or 5-HTTLPR) and STin2) on SSRI response. Studies were identified by the use of MEDLINE, EmBase and PsycINFO, references of articles, reviews and information from pharmaceutical companies. Nine studies assessing the influence of SERTPR or STin2 on treatment response were included. Outcome was expressed as the percentage of decrease in depression score (HAM-D or MADRS) or as the percentage of responders (> or =50% reduction on the depression scale). Both study methodologies and study outcomes showed large heterogeneity. Weighted mean decreases in depression score for patients with the s/s, s/l and l/l genotypes were 35.4, 46.3 and 48.0% at week 4, respectively, and 53.9, 54.6 and 48.3% at week 6. Among Caucasian patients, both mean decrease in depression score and response rate were lowest in the s/s group, while among Asian patients, results were inconsistent. Weighted response rates were 36.1% for the 10/12 genotype of the STin2 polymorphism and 80.7% for the 12/12 genotype (chi2=27.8, P<0.001) (only Asians). The available evidence points to a less favourable response to SSRI treatment among Caucasian patients with the SERTPR s/s genotype and among (Asian) patients with the STin2 10/12 genotype. In view of the scarcity and heterogeneity of the studies, however, current information is insufficiently reliable as a basis for implementing genetic testing in the diagnostic work-up of the depressive patient.     

5-羟色胺基因多态性与抑郁症的相关性研究

目的：探讨5-羟色胺转运体(5-HTT)基因启动子区多态性(5-HTTLPR)与抑郁症的相关性及其对抗抑郁药疗效的影响。方法：运用聚合酶链反应技术(PCR)检测51例抑郁症患者(患者组)和60名健康对照者(对照组)5-HTTLPR的分布频率；并予文拉法辛治疗，用汉密尔顿抑郁量表(HAMD)观察疗效。结果：患者组5-HTTLPR的短重复序列／短重复序列(short／short，S／S)基因型和短重复序列(short，S)等位基因频率分别为71％和81％，对照组为45％和69％差异显著。治疗4周后，长重复序列／长重复序列(long／long，L／L)基因型患者的减分率显著高于其他两型。结论：5-HTTLPR的S／S基因型可能是抑郁症的易感基因之一，L／L基因型可能和更好的选择性5-羟色胺受体阻滞剂类(SSRIs)疗效有关。     

No evidence for in vivo regulation of midbrain serotonin transporter availability by serotonin transporter promoter gene polymorphism.

BACKGROUND: A polymorphism in the serotonin transporter promoter gene region (5-HTTLPR) has been shown to influence the quantity of serotonin transporter expressed in human cell lines: the 5-HTTLPR short allele (s) has been associated with reduced 5-HTT expression when compared to cells carrying the 5-HTTLPR long allele (l). We performed a single photon emission computed tomography (SPECT) study using the ligand [(123)I]-2-beta-carbomethoxy-3-beta-(4-iodophenyl)tropane ([(123)I]-beta-CIT) to measure 5-HTT availability in 16 healthy subjects genotyped for 5-HTTLPR. METHODS: SPECT scans were performed 24 hours after tracer injection, regions of interest anatomically corresponding to the thalamus-hypothalamus and mesencephalon-pons areas were compared to the binding in the cerebellum, representing the nondisplaceable [(123)I]-beta-CIT-binding (results expressed as target activity minus cerebellum activity/cerebellum activity). DNA from peripheral nuclear blood cells was genotyped for 5-HTTLPR using standard polymerase chain reaction methods. RESULTS: Specific binding ratios in the thalamus-hypothalamus were 2.65 +/- 0.4 in subjects with the l/l genotype (n = 3), 2.76 +/- 0.5 in subjects with the l/s genotype (n = 9), and 2.77 +/- 0.4 in subjects with the s/s genotype (n = 4). Binding ratios in the mesencephalon-pons were 1.43 +/- 0.3 (l/l; n = 3), 1.37 +/- 0.3 (l/s; n = 9), and 1.28 +/- 0.3 (s/s; n = 4). None of these differences was statistically significant. CONCLUSIONS: Our data provide no evidence for in vivo functional regulation of 5-HTT availability by 5-HTTLPR in the thalamus-hypothalamus and mesencephalon-pons of healthy subjects.     

5-羟色胺转运体基因多态性与青少年抑郁症的关联研究

目的 探讨中国汉族青少年抑郁症与5-羟色胺转运体（5-HTY）基因的启动子区多态（5-HTTLPR）之间的关系。方法 应用聚合酶链式反应（PCR）扩增技术对84例青少年抑郁症患者和85例健康者进行基因型分析。结果 5-HTYLPR基因的3种基因型S／S,L／S和L/L在青少年抑郁症组的分布分别为57．1％,36．9％,6．0％;在对照组分别为57．6％,34．1％,8．2％,两组间差异无显著性（P〉0．05）。抑郁症组中S／S基因型患者HAMD自杀因子评分明显高于L／L和L／S型患者（P〈0.01）。结论 5-HTT基因多态性与青少年抑郁症无明显关联。抑郁症中携带S／S基因型患者的自杀风险相对比L／L型、L／S型患者高。     

强迫症与5-羟色胺转运体基因多态的关联分析

目的 探索汉族人群中5-羟色胺转运体SLC6A4基因多态与强迫症发病的关系。方法采用聚合酶链反应扩增片段长度多态技术测定120例强迫症患者(强迫症组)和130名健康人(对照组)的SLC6A4基因型。结果 强迫症组SLC6A4第2内含子及启动子的基因型多态分布与对照组间的差异有显著性(X2=6.70,P=0.035;X2=6.35,P=0.042);第2内含子等位基因频数分布与对照组之间的差异有非常显著性(X2=7.54,P=0.006);第2内含子的等位基因10,12/10基因型和启动子的L/L基因型与强迫症存在显著正关联[比数比(OR)值分别为2.24,2.12和3.57,P<0.05];强迫症组及对照组内不同性别间基因型分布的差异均无显著性(P>0.05)。结论 在汉族人群中SLC6A4基因可能与强迫症存在遗传关联,第2内含子的等位基因10和12/10基因型、启动子的L/L基因型可能是强迫症的风险因子。     

Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with selective serotonin reuptake inhibitor efficacy in depressed patients

The serotonin transporter gene promoter polymorphism (5-HTTLPR) has been repeatedly associated with antidepressant response in mood disorder patients, but findings are not consistent across studies. A meta-analysis was performed on 15 studies including data of 1435 subjects. We tested three phenotypes: remission rate, response rate and response rate within 4 weeks using the cochrane review manager. We observed a significant association of the s/s variant of 5-HTTLPR with remission rate (P<0.0001) and both s/s and s/l variants with response rate (P=0.0002). Response rate within 4 weeks was associated in both models (P=0.003-P<0.00001). This effect is quite robust to ethnic differences although a significant heterogeneity is present in Asian samples.