Novel 5-HTTLPR allele associates with higher serotonin transporter binding in putamen:: A [11C] DASB positron emission tomography study
Novel 5-HTTLPR allele associates with higher serotonin transporter binding in putamen:: A [11C] DASB positron emission tomography study
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DOI：
10.1016/j.biopsych.2006.09.022
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发表时间：
2007-08-15
影响因子：
10.6
通讯作者：
Meyer, Jeffrey H.
中科院分区：
文献类型：
--
作者：
Praschak-Rieder, Nicole;Kennedy, James;Meyer, Jeffrey H.
背景：5-羟色胺转运体(5-HTT)连锁多态区域(5-HTTLPR)有两个常见的等位基因，分别命名为长(L)和短(S)。在人类细胞系中，S等位基因与低水平的5-HTT mRNA和低水平的5-HTT表达有关。在L-A体内检测到一个功能性单核苷酸突变体，命名为L-A和L-A。在体外，只有L-A与5-羟色胺的高表达有关，而L-G是低表达的，更类似于S。我们用3-(11)C-amino-4-(2-dimethylaminomethylphenyl-sulfanyl)苯甲腈([C-11]DASB)正电子发射断层扫描检测了长(A/G)变异体对活体人脑中5-羟色胺F密度的可能影响。方法：对43例健康受试者进行5-HTTLPR长(A/G)基因分型，检测5-羟色胺结合势(5-HTT BP)。结果：L-A/L-A与壳核中较高的5-HTT BP相关(p=0.026，未校正)。这种关联在高加索亚组样本中变得更强(p=0.004)，即使在校正多次比较后仍显著。结论：在健康的高加索血统L-A/L-A携带者中，5-HTTLPR Long(A/G)多态性影响5-HTT密度，导致更高的壳蛋白5-HTT BP。这一发现将这种多态的作用从体外报道的L-A/L-A基因型的5-羟色胺高表达扩展到健康受试者的体内脑中。
Background: The serotonin transporter (5-HTT)-linked polymorphic region (5-HTTLPR) has two frequent alleles, designated long (L), and short (S). The S allele is associated with lower levels of 5-HTT mRNA and lower 5-HTT expression in human cell lines. A functional single nucleotide variant was detected within L-A designated L-A and L-A. Only L-A is associated with high levels of in vitro 5-HTT expression, whereas L-G is low expressing and more similar to S. We examined the possible influence of the long (A/G) variant on 5-HT-Fdensity in the living human brain using 3-(11)C-amino-4-(2-dimethylaminomethylphenyl-sulfanyl) benzonitrile ([C-11]DASB) positron emission tomography.Methods: The 5-HTT binding potential (5-HTT BP), an index of 5-HTT density, was found in 43 healthy subjects genotyped for 5-HTTLPR long (A/G), and in an ethnically homogenous subsample of 30 Caucasian-Canadians.Results: The L-A/L-A was associated with higher 5-HTT BP in putamen (p = .026, not corrected). This association became stronger in the Caucasian subsample (p = .004) and was significant even after correcting for multiple comparisons.Conclusions: The 5-HTTLPR long (A/G) polymorphism influences 5-HTT density leading to higher putamen 5-HTT BP in healthy L-A/L-A carriers of Caucasian ancestry. This finding extends the role of this polymorphism from in vitro reports of higher 5-HTT expression with the L-A/L-A genotype into in vivo brains of healthy human subjects.