Department of Animal Biology, Anthropology Section, Faculty of Biology, University of Barcelona, Spain.
Acta Psychiatr Scand. 2012 Mar;125(3):194-202. doi: 10.1111/j.1600-0447.2011.01764.x. Epub 2011 Sep 8.
The aims of this study were to test the individual association of the serotonin transporter gene (SLC6A4), the brain-derived neurotrophic factor gene (BDNF) and the GABA(A) α(6) receptor subunit gene (GABRA6) with anxiety-related traits and to explore putative gene-gene interactions in a Spanish healthy sample.
A sample of 937 individuals from the general population completed the Temperament and Character Inventory questionnaire to explore Harm Avoidance (HA) dimension; a subsample of 553 individuals also filled in the Big Five Questionnaire to explore the Neuroticism dimension. The whole sample was genotyped for the 5-HTTLPR polymorphism (SLC6A4 gene), the Val66Met polymorphism (BDNF gene) and the T1521C polymorphism (GABRA6 gene).
Homozygous individuals for the T allele of the T1512C polymorphism presented slightly higher scores for HA than C allele carriers (F = 2.96, P = 0.019). In addition, there was a significant gene-gene interaction on HA between the 5-HTTLPR and Val66Met polymorphisms (F = 3.4, P = 0.009).
GABRA6 emerges as a candidate gene involved in the variability of HA. The effect of a significant gene-gene interaction between the SLC6A4 and BDNF genes on HA could explain part of the genetic basis underlying anxiety-related traits.
本研究旨在检验 5-羟色胺转运体基因（SLC6A4）、脑源性神经营养因子基因（BDNF）和γ-氨基丁酸 A 型受体α6 亚单位基因（GABRA6）与焦虑相关特质的个体关联性，并探索西班牙健康人群中潜在的基因-基因相互作用。
一个由 937 名普通人群组成的样本完成了气质和性格问卷，以探讨回避特质（HA）维度；一个由 553 名个体组成的子样本也填写了大五人格问卷，以探讨神经质维度。对所有样本进行 5-HTTLPR 多态性（SLC6A4 基因）、Val66Met 多态性（BDNF 基因）和 T1521C 多态性（GABRA6 基因）的基因分型。
T1512C 多态性的 T 等位基因纯合子的 HA 得分略高于 C 等位基因携带者（F = 2.96，P = 0.019）。此外，5-HTTLPR 和 Val66Met 多态性之间存在显著的 HA 基因-基因相互作用（F = 3.4，P = 0.009）。
GABRA6 作为参与 HA 变异性的候选基因出现。SLC6A4 和 BDNF 基因之间显著的基因-基因相互作用对 HA 的影响可以解释焦虑相关特质遗传基础的一部分。
