Gelernter J, Kranzler H, Coccaro E F, Siever L J, New A S
Department of Psychiatry, VA Connecticut Healthcare System, West Haven Campus, 06516, USA.
Am J Psychiatry. 1998 Oct;155(10):1332-8. doi: 10.1176/ajp.155.10.1332.
The SLC6A4 locus encodes the serotonin transporter, which in turn mediates the synaptic inactivation of the neurotransmitter serotonin. A polymorphism located in the 5' promoter region of the gene is associated with altered transcriptional activity of SLC6A4; an earlier study reported an association of the polymorphism with anxiety- and depression-related traits, including harm avoidance and neuroticism. The authors attempted to replicate this finding.
They assessed genotype at the SLC6A4 promoter polymorphism, and an additional polymorphism in intron 2, in 322 American subjects of European and African ancestry, some with diagnoses of a personality disorder or substance dependence and some normal comparison subjects. Harm avoidance was measured by the Tridimensional Personality Questionnaire in all subjects, and neuroticism was measured by the NEO Five-Factor Inventory in 185 subjects. Allele frequencies in the groups were compared, and hierarchical multiple regression was used to examine the correlation of demographic features, psychiatric diagnostic group, and genotype with harm avoidance and neuroticism scores.
Although the demographic factors and psychiatric diagnoses had effects on harm avoidance and neuroticism scores, there was no main effect of genotype on these personality measures. In the context of these overall negative findings, interactions were observed between sex and promoter system genotype and between race and promoter system genotype which suggest that the present findings are not wholly inconsistent with those of the earlier study.
The authors were unable to replicate the association finding. The specific phenotypic composition of the groups studied with respect to other behaviors could have influenced ability to detect association of SLC6A4 polymorphisms with personality measures; population stratification for this locus is also of potential importance.
溶质载体家族6成员4（SLC6A4）基因座编码5-羟色胺转运体，该转运体进而介导神经递质5-羟色胺的突触失活。位于该基因5'启动子区域的一个多态性与SLC6A4转录活性的改变有关；一项早期研究报道该多态性与焦虑和抑郁相关性状有关，包括避免伤害和神经质。作者试图重复这一发现。
他们在322名欧洲和非洲裔美国受试者中评估了SLC6A4启动子多态性以及内含子2中的另一个多态性，其中一些受试者被诊断为患有精神障碍或物质依赖，还有一些是正常对照受试者。所有受试者均通过三维人格问卷测量避免伤害，185名受试者通过NEO五因素问卷测量神经质。比较了各组的等位基因频率，并使用分层多元回归分析人口统计学特征、精神科诊断组和基因型与避免伤害和神经质得分之间的相关性。
尽管人口统计学因素和精神科诊断对避免伤害和神经质得分有影响，但基因型对这些人格测量指标没有主要影响。在这些总体阴性结果的背景下，观察到性别与启动子系统基因型之间以及种族与启动子系统基因型之间存在相互作用，这表明目前的结果与早期研究结果并非完全不一致。
作者未能重复该关联发现。所研究组在其他行为方面的特定表型组成可能影响了检测SLC6A4多态性与人格测量指标之间关联的能力；该基因座的群体分层也可能具有重要意义。
