DNA methylation and single nucleotide variants in the brain-derived neurotrophic factor (BDNF) and oxytocin receptor (OXTR) genes are associated with anxiety/depression in older women.

DNA methylation and single nucleotide variants in the brain-derived neurotrophic factor (BDNF) and oxytocin receptor (OXTR) genes are associated with anxiety/depression in older women.
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DOI:
10.3389/fgene.2015.00230
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发表时间:
2015
影响因子:
3.7
通讯作者:
Préville M
Préville M
中科院分区:
生物学3区
文献类型:
--
作者:
Chagnon YC;Potvin O;Hudon C;Préville M

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背景资料:环境影响和个人经历可以通过表观遗传的非结构变化(如DNA甲基化)在个体中表达。这种甲基化可以上调或下调相应基因的表达,改变相关表型。DNA甲基化随着年龄的增长而增加,可能与某些形式的精神疾病的晚期表达有关。本研究的目的是评估老年妇女焦虑症和/或抑郁症与焦虑或抑郁症相关的四个基因的DNA甲基化之间的关联。方法:65岁及以上的女性(n = 19)或(n = 24)焦虑障碍和/或抑郁发作(DSM-IV),被招募。分别通过焦磷酸测序和PCR从唾液中评估以下基因的DNA甲基化和单核苷酸变体(SNV):脑源性神经营养因子(BDNF; rs6265)、催产素受体(OXTR; rs 53576)、5-羟色胺转运蛋白(SLC 6A 4; rs 25531)和载脂蛋白E(APOE; rs 429358和rs7412)。结果如下:与对照组受试者相比,在焦虑/抑郁受试者中观察到更大的BDNF DNA甲基化(平均值:2.92 SD ± 0.74 vs. 2.34 ± 0.42; p= 0.0026)。这种差异在携带BDNF rs6265 CT基因型的受试者中(2.99 ± 0.41 vs. 2.27 ± 0.26; p= 0.0006)比携带CC基因型的受试者(p= 0.0332)更明显;没有观察到TT基因型的受试者。对于OXTR,在患有焦虑/抑郁的受试者中观察到更大的DNA甲基化,但仅对于携带OXTR rs 53576 SNV的AA基因型的受试者,更特别地在所研究的七个CpG中的一个处(7.01 ± 0.94对4.44 ± 1.11; p= 0.0063)。APOE和SLC 6A 4没有观察到显著差异。结论:这些结果表明,DNA甲基化与BDNF和OXTR的SNV变异相互作用,与老年妇女焦虑/抑郁的发生有关。
Background: Environmental effects and personal experiences could be expressed in individuals through epigenetic non-structural changes such as DNA methylation. This methylation could up- regulate or down-regulate corresponding gene expressions and modify related phenotypes. DNA methylation increases with aging and could be related to the late expression of some forms of mental disease. The objective of this study was to evaluate the association between anxiety disorders and/or depression in older women and DNA methylation for four genes related to anxiety or depression. Methods: Women aged 65 and older with (n = 19) or without (n = 24) anxiety disorders and/or major depressive episode (DSM-IV), were recruited. DNA methylation and single nucleotide variant (SNV) were evaluated from saliva, respectively by pyrosequencing and by PCR, for the following genes: brain-derived neurotrophic factor (BDNF; rs6265), oxytocin receptor (OXTR; rs53576), serotonin transporter (SLC6A4; rs25531), and apolipoprotein E (APOE; rs429358 and rs7412). Results: A greater BDNF DNA methylation was observed in subjects with anxiety/depression compared to control group subjects (Mean: 2.92 SD ± 0.74 vs. 2.34 ± 0.42; p= 0.0026). This difference was more pronounced in subjects carrying the BDNF rs6265 CT genotype (2.99 ± 0.41 vs. 2.27 ± 0.26; p= 0.0006) than those carrying the CC genotype (p= 0.0332); no subjects with the TT genotype were observed. For OXTR, a greater DNA methylation was observed in subjects with anxiety/depression, but only for those carrying the AA genotype of the OXTR rs53576 SNV, more particularly at one out of the seven CpGs studied (7.01 ± 0.94 vs. 4.44 ± 1.11; p= 0.0063). No significant differences were observed for APOE and SLC6A4. Conclusion: These results suggest that DNA methylation in interaction with SNV variations in BDNF and OXTR, are associated with the occurrence of anxiety/depression in older women.
DOI: 10.1371/journal.pone.0006767
发表时间: 2009-08-26
期刊: PloS one
影响因子: 3.7
作者:
Boks MP;Derks EM;Weisenberger DJ;Strengman E;Janson E;Sommer IE;Kahn RS;Ophoff RA
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期刊: PLoS genetics
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