Juckel Georg, Kawohl Wolfram, Giegling Ina, Mavrogiorgou Paraskevi, Winter Christine, Pogarell Oliver, Mulert Christoph, Hegerl Ulrich, Rujescu Dan
Department of Psychiatry, Ruhr-University Bochum, Germany.
Hum Psychopharmacol. 2008 Mar;23(2):115-20. doi: 10.1002/hup.906.
The loudness dependence of auditory evoked potentials (LDAEP) provides a measure of the central serotonergic activity. As dopamine transporter availabilities also correlate with LDAEP, a dopaminergic influence is probable. The enzyme catechol-O-methyltransferase (COMT) is involved in the inactivation of synaptic dopamine. The aim of this study was to investigate the relationship between genetic variants of the COMT gene influencing synaptic dopamine levels and the LDAEP.
Rs737865 in intron 1, rs4680 coding for a Val158Met substitution and rs165599 in the 3' region were investigated in 95 carefully selected healthy subjects of German descent (41 males, 54 females). The LDAEP was calculated as a linear regression slope with stimulus intensity as independent and N1/P2-amplitude as dependent variables.
Single marker analysis showed weak associations for two single nucleotide polymorphisms (SNPs) (rs737865: CC vs. T allele carrier; rs4680: G-allele carrier vs. AA homozygotes). A-G (rs4680-rs165599) was associated with lower LDAEP scores. Accordingly, haplotype analysis with all SNPs (rs737865-rs4680-rs165599) showed that the T-A-G haplotype was associated with lower scores.
These findings support the hypothesis that the LDAEP is also influenced by dopaminergic transmission. However, replications of these very preliminary but potentially important findings in independent samples are needed.
听觉诱发电位的响度依赖性（LDAEP）可衡量中枢5-羟色胺能活性。由于多巴胺转运体可用性也与LDAEP相关，因此可能存在多巴胺能影响。儿茶酚-O-甲基转移酶（COMT）参与突触多巴胺的失活。本研究旨在探讨影响突触多巴胺水平的COMT基因遗传变异与LDAEP之间的关系。
对95名精心挑选的德国血统健康受试者（41名男性，54名女性）进行研究，检测其1号内含子中的Rs737865、编码Val158Met替代的rs4680以及3'区域中的rs165599。LDAEP计算为以刺激强度为自变量、N1/P2振幅为因变量的线性回归斜率。
单标记分析显示，两个单核苷酸多态性（SNP）存在弱关联（rs737865：CC与T等位基因携带者；rs4680：G等位基因携带者与AA纯合子）。A-G（rs4680-rs165599）与较低的LDAEP评分相关。因此，对所有SNP（rs737865-rs4680-rs165599）进行单倍型分析表明，T-A-G单倍型与较低评分相关。
这些发现支持了LDAEP也受多巴胺能传递影响的假说。然而，需要在独立样本中重复这些非常初步但可能重要的发现。
