Mazzanti C M, Lappalainen J, Long J C, Bengel D, Naukkarinen H, Eggert M, Virkkunen M, Linnoila M, Goldman D
Laboratory of Neurogenetics, National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD 20852, USA.
Arch Gen Psychiatry. 1998 Oct;55(10):936-40. doi: 10.1001/archpsyc.55.10.936.
The heritability of interindividual variation in anxiety and other aspects of personality establishes that variants of genes influence these traits. A functional polymorphism in the promoter of the human serotonin transporter gene (SLC6A4C) was identified and found to be linked to an anxiety-related personality trait, Neuroticism. The polymorphism affects gene transcription and, ultimately, gene function. We have attempted to confirm the role of SLC6A4C in anxiety-related personality traits by sibpair analysis and association studies.
Sibpair linkage analysis and association study were performed in 655 Finns. The index cases were 182 alcoholic criminal offenders, through which 258 relatives were ascertained to obtain 366 sibpairs. In addition, 215 unrelated population controls were collected. Each individual was psychiatrically interviewed, blind-rated for DSM-III-R diagnoses, and assessed with the Tridimensional Personality Questionnaire.
The sibpair analysis revealed a positive linkage between SLC6A4C and the 2 anxiety-related subdimensions of Harm Avoidance: HA1 (Anticipatory Worry) and HA2 (Fear of Uncertainty) (P = .003). However, there was no consistent association between SLC6A4C and any Tridimensional Personality Questionnaire trait.
In the present study we replicated the relationship of SLC6A4C to anxiety by sibpair linkage analysis but found no evidence of association, raising the question of whether SLC6A4C locus is itself affecting anxiety or is linked to another still unknown functional variant.
焦虑及人格其他方面个体间变异的遗传力表明基因变异会影响这些特质。已鉴定出人类血清素转运体基因（SLC6A4C）启动子中的一个功能性多态性，并发现其与一种焦虑相关的人格特质——神经质有关。该多态性影响基因转录，最终影响基因功能。我们试图通过同胞对分析和关联研究来证实SLC6A4C在焦虑相关人格特质中的作用。
对655名芬兰人进行同胞对连锁分析和关联研究。索引病例为182名酒精成瘾的刑事罪犯，通过他们确定了258名亲属，从而获得366个同胞对。此外，还收集了215名无亲缘关系的人群对照。对每个个体进行精神病学访谈，采用盲法评定DSM-III-R诊断，并使用三维人格问卷进行评估。
同胞对分析显示SLC6A4C与回避伤害的2个焦虑相关子维度之间存在正连锁关系：HA1（预期性担忧）和HA2（对不确定性的恐惧）（P = 0.003）。然而，SLC6A4C与任何三维人格问卷特质之间均无一致的关联。
在本研究中，我们通过同胞对连锁分析重现了SLC6A4C与焦虑的关系，但未发现关联证据，这就提出了一个问题，即SLC6A4C位点本身是否影响焦虑，或者是否与另一个仍未知的功能变异相关联。
