Acetylcholinesterase/paraoxonase genotype and expression predict anxiety scores in health, risk factors, exercise training, and genetics study
Acetylcholinesterase/paraoxonase genotype and expression predict anxiety scores in health, risk factors, exercise training, and genetics study
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DOI：
10.1073/pnas.0307659101
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发表时间：
2004-04-13
影响因子：
11.1
通讯作者：
Soreq, H
中科院分区：
文献类型：
--
作者：
Sklan, EH;Lowenthal, A;Soreq, H
焦虑涉及基因组，环境和经验衍生因素的复杂，不完全理解的相互作用，目前正在通过心理学标准进行测量。在这里，我们报告以前未察觉的表达变异和染色体7 q21 -22乙酰胆碱酯酶-对氧磷酶1（ACHE-PON 1）基因座的核苷酸多态性与特质和状态焦虑的措施，461名健康受试者的健康，危险因素，运动训练和遗传学家庭研究之间的相互关系。AChE蛋白控制应激增强的乙酰胆碱信号传导的终止，而PON蛋白显示过氧化物酶样活性，从而保护血液蛋白免受氧化应激损伤。血清乙酰胆碱酯酶和PON酶活性都被发现受人口统计学参数，并表现出相反的，相互关联的焦虑措施。此外，状态焦虑的瞬时得分和特质焦虑的易感性得分似乎都与酶活性有关。这一发现支持了相应基因表达关系的概念。ACHE和PON 1基因的平行多态性与特质焦虑和状态焦虑评分有明显的相关性。我们的研究结果表明，焦虑情绪的一个重要来源涉及遗传和后天的乙酰胆碱调节参数，这些参数可以很容易地量化，这可以帮助解释状态和特质焦虑的部分人类差异。
Anxiety involves complex, incompletely understood interactions of genomic, environmental, and experience-derived factors, and is currently being measured by psychological criteria. Here, we report previously nonperceived interrelationships between expression variations and nucleotide polymorphisms of the chromosome 7q21-22 acetylcholinesterase-paraoxonase 1 (ACHE-PON1) locus with the trait- and state-anxiety measures of 461 healthy subjects from the Health, Risk Factors, Exercise Training, and Genetics Family Study. The AChE protein controls the termination of the stress-enhanced acetylcholine signaling, whereas the PON protein displays peroxidase-like activity, thus protecting blood proteins from oxidative stress damages. Serum AChE and PON enzyme activities were both found to be affected by demographic parameters, and showed inverse, reciprocal associations with anxiety measures. Moreover, the transient scores of state anxiety and the susceptibility score of trait anxiety both appeared to be linked to enzyme activities. This finding supported the notion of corresponding gene expression relationships. Parallel polymorphisms in the ACHE and PON1 genes displayed apparent associations with both trait- and state-anxiety scores. Our findings indicate that a significant source of anxiety feelings involves inherited and acquired parameters of acetylcholine regulation that can be readily quantified, which can help explaining part of the human variance for state and trait anxiety.