AGTR1 gene variation: association with depression and frontotemporal morphology.
AGTR1 gene variation: association with depression and frontotemporal morphology.
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DOI：
10.1016/j.pscychresns.2012.03.007
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发表时间：
2012-05-31
影响因子：
11.3
通讯作者：
Ashley-Koch A
中科院分区：
文献类型：
--
作者：
Taylor WD;Benjamin S;McQuoid DR;Payne ME;Krishnan RR;MacFall JR;Ashley-Koch A
肾素-血管紧张素系统（RAS）与生理和心理应激反应有关，但其在应激相关精神疾病中的作用尚不清楚。我们研究了AGTR 1（编码1型血管紧张素II受体（AT 1 R）的基因）的变异是否与抑郁症的诊断以及白色物质高信号和额颞叶脑体积的差异相关。257名抑郁症和116名非抑郁症老年白人受试者完成了临床评估，并提供了用于基因分型的血液样本。我们利用单倍型标记单核苷酸多态性（htSNP）分析来测试AGTR 1的变异。281名受试者获得了用于测量高信号病变的1.5T MRI数据，而70名受试者完成了3 T MRI，允许测量海马和背外侧前额叶皮质（dlPFC）。两个htSNP在诊断队列之间表现出统计学显著的频率差异：rs 10935724和rs 12721331。虽然高信号病变体积没有显着不同的任何htSNP，dlPFC和海马体积显着不同的几个htSNP。有趣的是，对于dlPFC和海马体积显著不同的那些htSNP，与较小dlPFC体积相关的变体与较大海马体积相关。这支持了AGTR 1的遗传变异与抑郁症和额颞叶形态差异有关。
The renin-angiotensin system (RAS) is implicated in the response to physiological and psychosocial stressors however its role in stress-related psychiatric disorders is poorly understood. We examined if variation in AGTR1, the gene coding for the type 1 angiotensin II receptor (AT1R), is associated with a diagnosis of depression and differences in white matter hyperintensities and frontotemporal brain volumes. 257 depressed and 116 nondepressed elderly Caucasian subjects completed clinical assessments and provided blood samples for genotyping. We utilized a haplotype-tagging single nucleotide polymorphism (htSNP) analysis to test for variation in AGTR1. 1.5T MRI data for measurement of hyperintense lesions were available on 281 subjects, while 70 subjects completed 3T MRI allowing for measurements of the hippocampus and dorsolateral prefrontal cortex (dlPFC). Two htSNPs exhibited statistically significant frequency differences between diagnostic cohorts: rs10935724 and rs12721331. Although hyperintense lesion volume did not significantly differ by any htSNP, dlPFC and hippocampus volume differed significantly for several htSNPs. Intriguingly, for those htSNPs differing significantly for both dlPFC and hippocampus volume, the variant associated with smaller dlPFC volume was associated with larger hippocampal volume. This supports that genetic variation in AGTR1 is associated with depression and differences in frontotemporal morphology.