Costa Barbara, Pini Stefano, Baldwin David S, Silove Derrick, Manicavasagar Vijaya, Abelli Marianna, Coppedè Fabio, Martini Claudia
Department of Pharmacy, University of Pisa, Pisa, Italy.
Department of Clinical and Experimental Medicine, Section of Psychiatry, University of Pisa, Pisa, Italy.
J Affect Disord. 2017 Aug 15;218:365-373. doi: 10.1016/j.jad.2017.03.056. Epub 2017 Mar 27.
The impact of combined variants of Oxytocin Receptor (OXTR) and G protein β3 subunit genes was investigated in relation to retrospective reports of childhood as well as contemporary adult separation anxiety (SA), based on evidence of a β/γ dimer-mediated signaling for OXTR.
A case-control association study (225 healthy adults and 188 outpatients with depression) was performed to establish Risk-Combined Genotype (RCG) of the studied variants (OXTR rs53576 and the functional Gβ3 subunit rs5443). Current SA was evaluated by the ASA-27 and retrospective childhood symptoms by the SASI. GG genotype of OXTR rs53576 combined with T-carrier genotype of Gβ3 rs5443 represented the RCG.
Compared to non-RCG, those with RCG had significantly higher levels of childhood and adult SA. The RCG was significantly associated with childhood SA threshold score (OR=2.85, 90%CI: 1.08-7.50). Childhood SA was, in turn, strongly associated with a threshold SA score in adulthood (OR=15.58; 95% CI: 4.62-52.59).
Although the overall sample size is sizable, comparisons among subgroups with specific combination of alleles are based on relatively small numbers.
Our study indicates that variations in OXTR and Gβ3 genes are specifically associated with presence and severity of SA in childhood and adulthood, but not with depression or anxiety in general. Because there is increasing interest in oxytocin in social behavior, the gene-SA associations identified have potential translational and clinical relevance.
基于催产素受体（OXTR）的β/γ二聚体介导信号传导的证据，研究了OXTR和G蛋白β3亚基基因的联合变体与儿童期回顾性报告以及当代成人分离焦虑（SA）之间的关系。
进行了一项病例对照关联研究（225名健康成年人和188名抑郁症门诊患者），以确定所研究变体（OXTR rs53576和功能性Gβ3亚基rs5443）的风险联合基因型（RCG）。通过ASA - 27评估当前的SA，通过SASI评估儿童期回顾性症状。OXTR rs53576的GG基因型与Gβ3 rs5443的T携带者基因型代表RCG。
与非RCG相比，具有RCG的个体在儿童期和成人期的SA水平显著更高。RCG与儿童期SA阈值评分显著相关（OR = 2.85，90%CI：1.08 - 7.50）。反过来，儿童期SA与成年期的SA阈值评分密切相关（OR = 15.58；95%CI：4.62 - 52.59）。
尽管总体样本量较大，但等位基因特定组合亚组之间的比较基于相对较小的数量。
我们的研究表明，OXTR和Gβ3基因的变异与儿童期和成年期SA的存在及严重程度特别相关，但与一般的抑郁或焦虑无关。由于社会行为中对催产素的兴趣日益增加，所确定的基因与SA的关联具有潜在的转化和临床意义。
