Central serotonin transporter availability measured with [123I]beta-CIT SPECT in relation to serotonin transporter genotype.
Central serotonin transporter availability measured with [123I]beta-CIT SPECT in relation to serotonin transporter genotype.
复制标题
使用 [123I]beta-CIT SPECT 测量与血清素转运蛋白基因型相关的中枢血清素转运蛋白可用性。
DOI：
10.1176/appi.ajp.161.3.525
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Gelernter,Joel
中科院分区：
文献类型：
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作者：
vanDyck,ChristopherH;Malison,RobertT;Staley,JulieK;Jacobsen,LeslieK;Seibyl,JohnP;Laruelle,Marc;Baldwin,RonaldM;Innis,RobertB;Gelernter,Joel
在编码5-羟色胺转运蛋白（SERT）的基因（SLC 6A 4）的启动子区描述了一种功能多态性。这种多态性有两个常见的等位基因，称为长和短。每个等位基因都与许多人类临床表型相关，包括与5-羟色胺传递失调相关的神经精神疾病。对非神经细胞的体外研究表明，长等位基因可能比短等位基因具有更高的转录活性。然而，这些发现的相关性SERT水平在brain.METHODThe作者评估基因型在SLC 6A 4启动子多态性在96名健康的欧洲裔美国人进行单光子发射计算机断层扫描与[123 I]2β-carbomethoxy-3β-（4-iodophenyl）tropane（[123 I]β-CIT）测量中央SERT的可用性。特异性脑摄取与不可替代脑摄取的比率（即，V3′′=[脑干-间脑-枕叶]/枕叶），与结合电位（Bmax/KD）成正比。事后Tukey成对比较显示，短-短纯合子比长-短杂合子具有显著更大的SERT可用性。有一个非显着的趋势，长-长的纯合子有更大的SERT可用性比杂合子，但没有观察到长-长的纯合子和短-短的纯合子之间的差异。年龄的影响是显着的协方差model.CONCLUSIONSThese结果的分析并不表明较高的中央SERT水平与长等位基因在欧洲裔美国人的主题，但指向一个更复杂的关系SLC 6A 4基因型和蛋白质的可用性。
OBJECTIVEA functional polymorphism has been described in the promoter region of the gene (SLC6A4) coding for the serotonin transporter protein (SERT). This polymorphism has two common alleles, designated as long and short. Each allele has been linked with a number of human clinical phenotypes, including neuropsychiatric diseases associated with dysregulation of serotonin transmission. In vitro studies of nonneural cells have suggested that the long allele may have higher transcriptional activity than the short allele. However, the relevance of these findings for SERT levels in the brain remains unclear.METHODThe authors assessed genotypes at the SLC6A4 promoter polymorphism in 96 healthy European American subjects who underwent single photon emission computed tomography scanning with [123I]2β-carbomethoxy-3β-(4-iodophenyl) tropane ([123I]β-CIT) for measurement of central SERT availability. A ratio of specific to nondisplaceable brain uptake (i.e., V3′′=[brainstem-diencephalon – occipital]/occipital), a measure proportional to the binding potential (Bmax/KD), was derived.RESULTSThe results showed that the main effect of genotype was significant. Post hoc Tukey pairwise comparisons revealed that the short-short homozygotes had significantly greater SERT availability than the long-short heterozygotes. There was a nonsignificant tendency for the long-long homozygotes to have greater SERT availability than the heterozygotes, but no difference was observed between the long-long homozygotes and the short-short homozygotes. The effect of age was significant in the analysis of covariance model.CONCLUSIONSThese results do not suggest higher central SERT levels in association with the long allele in European American subjects but point to a more complex relationship between SLC6A4 genotype and protein availability.