带状疱疹神经痛全基因组及GCH1基因甲基化差异变化研究

doi:10.3760/cma.j.issn.0412-4030.2019.06.009

中华皮肤科杂志 ›› 2019, Vol. 52 ›› Issue (6): 420-424.doi: 10.3760/cma.j.issn.0412-4030.2019.06.009

带状疱疹神经痛全基因组及GCH1基因甲基化差异变化研究

杨肖肖¹ 郑娜娜¹ 钟连生¹ 潘志强² 郁泽宇³

¹徐州医科大学附属医院皮肤性病科 221002；²徐州医科大学麻醉学重点实验室 221002；³徐州医科大学形态学科研实验中心 221002

收稿日期:2018-06-21 修回日期:2019-04-09 发布日期:2019-06-03
通讯作者: 钟连生 E-mail:zhongliansheng73@sina.com

Changes in methylation status of the whole genome and GCH1 gene in patients with herpes zoster neuralgia

Yang Xiaoxiao¹, Zheng Na′na¹, Zhong Liansheng¹, Pan Zhiqiang², Yu Zeyu³

¹Department of Dermatology and Venereology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu, China; ²Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou 221002, Jiangsu, China; ³Morphological Research Experiment Center, Xuzhou Medical University, Xuzhou 221002, Jiangsu, China

Received:2018-06-21 Revised:2019-04-09 Published:2019-06-03
Contact: Zhong Liansheng E-mail:zhongliansheng73@sina.com

摘要/Abstract

摘要： 【摘要】目的探讨全基因组及GCH1基因甲基化水平与带状疱疹神经痛的相关性。方法选择2017年6－10月在徐州医学科大学附属医院皮肤科确诊为带状疱疹且有明显神经痛症状的患者，经抗病毒和营养神经等药物治疗后疼痛完全缓解，以不影响正常睡眠为标准。最终入选36例患者及同期36例健康对照。取患者治疗前后及健康对照者外周血，斑点杂交实验检测全基因组甲基化水平的变化，甲基化DNA富集试剂盒富集GCH1基因甲基化区域，实时定量PCR技术检测GCH1基因甲基化水平的变化。采用GraphPad Prism v7.00软件对实验数据进行统计分析，带状疱疹患者治疗前后比较应采用配对t检验，而患者组与健康对照组比较采用两独立样本t检验。结果带状疱疹神经痛患者治疗前组、治疗后组及健康对照组全基因组相对甲基化水平分别为135.94 ± 2.52、144.76 ± 3.48、146.84 ± 3.39，治疗前组显著低于治疗后组（t = 2.056，P < 0.05）及健康对照组（t = 2.580，P < 0.05），而治疗后组与健康对照组差异无统计学意义（t = 0.429，P > 0.05）。治疗前组、治疗后组及健康对照组GCH1相对甲基化水平分别为0.65 ± 0.17、0.89 ± 0.13、0.97 ± 0.07，治疗前组显著低于治疗后组（t = 3.977，P < 0.05）及健康对照组（t = 4.648，P < 0.01），而治疗后组与健康对照组差异无统计学意义（t = 0.506，P > 0.05）。结论带状疱疹神经痛患者组全基因组及GCH1基因甲基化水平降低。

关键词: 神经痛, 带状疱疹后；甲基化；表观基因组学； GCH1基因

Abstract: 【Abstract】 Objective To analyze the correlation between herpes zoster neuralgia and the methylation status of the whole genome and GCH1 gene. Methods From June to October in 2017, patients with confirmed herpes zoster and obvious neuralgia were selected in Department of Dermatology, The Affiliated Hospital of Xuzhou Medical University, who achieved complete remission （no effect was observed on normal sleep） of neuralgia after antiviral and neurotrophic treatment. Finally, 36 patients and 36 healthy controls were enrolled into this study. Peripheral blood samples were obtained from the healthy controls and patients before and after the treatment. Dot-blot hybridization assay was performed to determine the methylation status of the whole genome, methylated-DNA IP kit was used to enrich the methylation sites of the GCH1 gene, and real-time quantitative PCR was conducted to detect changes in methylation status of the GCH1 gene. Statistical analysis was carried out with GraphPad Prism v7.00 software by using paired t test for the comparison of methylation status before and after the treatment, and two-sample t test for the comparison between the patient group and control group. Results The relative methylation level of the whole genome was 135.94 ± 2.52 in the patients before treatment, significantly lower than that in the patients after treatment （144.76 ± 3.48, t = 2.056, P < 0.05） and healthy control group （146.84 ± 3.39, t = 2.580, P < 0.05）. However, there was no significant difference in the methylation status of the whole genome between the patients after treatment and healthy controls （t = 0.429, P > 0.05）. Compared with the patients after treatment （0.89 ± 0.13） and healthy control group （0.97 ± 0.07）, the methylation status of the GCH1 gene significantly decreased in the patients before treatment （0.65 ± 0.17; t = 3.977, 4.648 respectively, P < 0.05, < 0.01 respectively）, while no significant difference between the patients after treatment and the healthy controls （t = 0.506, P > 0.05）. Conclusion The methylation status of the whole genome and GCH1 gene markedly decreased in the patients with herpes zoster neuralgia.

Key words: Neuralgia, postherpetic, Methylation, Epigenomics, GCH1 gene

杨肖肖郑娜娜钟连生潘志强郁泽宇. 带状疱疹神经痛全基因组及GCH1基因甲基化差异变化研究[J]. 中华皮肤科杂志, 2019,52(6):420-424. doi:10.3760/cma.j.issn.0412-4030.2019.06.009

Yang Xiaoxiao, Zheng Na′na, Zhong Liansheng, Pan Zhiqiang, Yu Zeyu. Changes in methylation status of the whole genome and GCH1 gene in patients with herpes zoster neuralgia[J]. Chinese Journal of Dermatology, 2019, 52(6): 420-424.doi:10.3760/cma.j.issn.0412-4030.2019.06.009

参考文献 25

［1］	Penas C, Navarro X. Epigenetic modifications associated to neuroinflammation and neuropathic pain after neural trauma［J］. Front Cell Neurosci, 2018,12:158. doi: 10.3389/fncel.2018.00158.
［2］	Portela A, Esteller M. Epigenetic modifications and human disease［J］. Nat Biotechnol, 2010,28（10）:1057⁃1068. doi: 10. 1038/nbt.1685.
［3］	Klose RJ, Bird AP. Genomic DNA methylation: the mark and its mediators［J］. Trends Biochem Sci, 2006,31（2）:89⁃97. doi: 10. 1016/j.tibs.2005.12.008.
［4］	Tajerian M, Alvarado S, Millecamps M, et al. DNA methylation of SPARC and chronic low back pain［J］. Mol Pain, 2011,7:65. doi: 10.1186/1744⁃8069⁃7⁃65.
［5］	Viet CT, Ye Y, Dang D, et al. Re⁃ of the methylated EDNRB gene in oral squamous cell carcinoma attenuates cancer⁃induced pain［J］. Pain, 2011,152（10）:2323⁃2332. doi: 10.1016/j.pain.2011.06.025.
［6］	Odell DW. Epigenetics of pain mediators［J］. Curr Opin Anaesthesiol, 2018,31（4）:402⁃406. doi: 10.1097/ACO.0000000 000000613.
［7］	Xiao HS, Huang QH, Zhang FX, et al. Identification of gene profile of dorsal root ganglion in the rat peripheral axotomy model of neuropathic pain［J］. Proc Natl Acad Sci U S A, 2002,99（12）:8360⁃8365. doi: 10.1073/pnas.122231899.
［8］	Young EE, Lariviere WR, Belfer I. Genetic basis of pain variability: recent advances［J］. J Med Genet, 2012,49（1）:1⁃9. doi: 10.1136/jmedgenet⁃2011⁃100386.
［9］	张闻, 郑多. 医学生物学［M］. 北京: 中国医药科技出版社, 2016:105.
［10］	Robertson KD. DNA methylation and human disease［J］.Nature Reviews Genetics, 2005,6（8）:597⁃610. doi: 10.1038/nrg 1655.
［11］	Zhang HH, Hu J, Zhou YL, et al. Promoted interaction of nuclear factor⁃κB with demethylated purinergic P2X3 receptor gene contributes to neuropathic pain in rats with diabetes［J］. Diabetes, 2015,64（12）:4272⁃4284. doi: 10.2337/db15⁃0138.
［12］	Feng W, Teng R, Zhao Y, et al. Epigenetic modulation of Wnt signaling contributes to neuropathic pain in rats［J］. Mol Med Rep, 2015,12（3）:4727⁃4733. doi: 10.3892/mmr.2015.3972.
［13］	Jiang BC, He LN, Wu XB, et al. Promoted interaction of C/EBPα with demethylated Cxcr3 gene promoter contributes to neuropathic pain in mice［J］. J Neurosci, 2017,37（3）:685⁃700. doi: 10.1523/JNEUROSCI.2262⁃16.2016.
［14］	Wang Y, Liu C, Guo QL, et al. Intrathecal 5⁃azacytidine inhibits global DNA methylation and methyl⁃ CpG⁃binding protein 2 and alleviates neuropathic pain in rats following chronic constriction injury［J］. Brain Res, 2011,1418:64⁃69. doi: 10.1016/j.brainres.2011.08.040.
［15］	Guedon JM, Yee MB, Zhang M, et al. Neuronal changes induced by varicella zoster virus in a rat model of postherpetic neuralgia［J］. Virology, 2015,482:167⁃180. doi: 10.1016/j.virol.2015.03. 046.
［16］	于雪, 刘妍, 万成福, 等. 中国北方汉族人群PHN发病与HLA⁃A等位基因相关性研究［J］. 中国疼痛医学杂志, 2016,22（5）:360⁃363. doi: 10.3969/j.issn.1006⁃9852.2016.05.009.
［17］	梁啸, 刘洪美, 李庆伟, 等. 对SNI和CCI两种大鼠神经病理性疼痛模型的实验观察［J］. 济宁医学院学报, 2013,36（1）:22⁃24,27. doi: 10.3969/j.issn.1000⁃9760.2013.01.005.
［18］	Kim SJ, Lee WI, Lee YS, et al. Effective relief of neuropathic pain by adeno⁃associated virus⁃mediated of a small hairpin RNA against GTP cyclohydrolase 1［J］. Mol Pain, 2009,5:67. doi: 10.1186/1744⁃8069⁃5⁃67.
［19］	Widschwendter M, Apostolidou S, Raum E, et al. Epigenotyping in Peripheral Blood Cell DNA and Breast Cancer Risk: A Proof of Principle Study［J］. PLoS ONE, 2008,3（7）:e2656. doi: 10.1371/ journal.pone.0002656.
［20］	Wang C, Chen L, Yang Y, et al. Identification of potential blood biomarkers for Parkinson′s disease by gene and DNA methylation data integration analysis［J］. Clin Epigenetics, 2019,11（1）:24.doi:10.1186/s13148⁃019⁃0621⁃5.
［21］	Kang Q, Jin P, Yang L, et al. Significance of Septin9 gene methylation detection of plasma circulation DNA in colorectal cancer screening［J］. Zhonghua Yi Xue Za Zhi, 2014,94（48）:3839⁃3841.doi:10.3760/ema.j.issn.0376⁃2491.2014.48.012.
［22］	Skuladottir GV, Nilsson EK, Mwinyi J, et al. One⁃night sleep deprivation induces changes in the DNA methylation and serum activity indices of stearoyl⁃CoA desaturase in young healthy men［J］. Lipids Health Dis, 2016,15（1）:137. doi: 10.1186/s12944⁃016⁃0309⁃1.
［23］	Henderson⁃Smith A, Fisch KM, Hua J, et al. DNA methylation changes associated with Parkinson′s disease progression: outcomes from the first longitudinal genome⁃wide methylation analysis in blood［J］. Epigenetics, 2019,3（14）:1⁃18. doi: 10.1080/ 15592294.2019.158 8682.
［24］	Zhang Q, Sun X, Xiao X, et al. Dietary Chromium Restriction of Pregnant Mice Changes the Methylation Status of Hepatic Genes Involved with Insulin Signaling in Adult Male Offspring［J/OL］. Plos One, 2017,12（1）:e0169889.
［25］	Ren J, Cheng Y, Ming ZH, et al. Intrauterine hyperglycemia exposure results in intergenerational inheritance via DNA methylation reprogramming on F1 PGCs［J］. Epigenetics Chromatin, 2018,11（1）:20. doi: 10.1186/s13072⁃018⁃0192⁃2.

[1]	中华医学会皮肤性病学分会中国康复医学会皮肤病康复专业委员会中国中西医结合学会皮肤性病学分会中国医药教育协会皮肤病专业委员会. 老年带状疱疹诊疗专家共识[J]. 中华皮肤科杂志, 2023, 56(2): 97-104.
[2]	李安琪孙秋宁. 脑源性神经营养因子与皮肤病[J]. 中华皮肤科杂志, 2023, 0(2): 20210746-e20210746.
[3]	杨玉凤李艳红王雨辉闫润润孙文娟段毅飞李妍. 电刺激和重复经颅磁刺激在带状疱疹后神经痛中的应用现状[J]. 中华皮肤科杂志, 2023, 56(1): 86-89.
[4]	中国医师协会皮肤科医师分会带状疱疹专家共识工作组国家皮肤与免疫疾病临床医学研究中心. 中国带状疱疹诊疗专家共识（2022版）[J]. 中华皮肤科杂志, 2022, 55(12): 1033-1040.
[5]	张元文孙从乾潘文东. 肉毒毒素在皮肤科的超适应证临床应用[J]. 中华皮肤科杂志, 2022, 0(1): 20210389-e20210389.
[6]	向睿宇李锁冯素英. 普瑞巴林在皮肤科的应用进展[J]. 中华皮肤科杂志, 2020, 53(3): 233-235.
[7]	何彩凤慈超唐彪常小丽强娣季必华. 播散性带状疱疹53例临床特点分析[J]. 中华皮肤科杂志, 2016, 49(11): 806-809.
[8]	赖亭吉施和建. 加巴喷丁联合糖皮质激素治疗带状疱疹神经痛的疗效观察[J]. 中华皮肤科杂志, 2012, 45(2): 145-146.
[9]	顾菊林温海刘训荃郑志忠顾军. 加巴喷丁胶囊治疗疱疹后神经痛的多中心临床观察[J]. 中华皮肤科杂志, 2009, 42(7): 451-454.

带状疱疹神经痛全基因组及GCH1基因甲基化差异变化研究

Changes in methylation status of the whole genome and GCH1 gene in patients with herpes zoster neuralgia

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献 25

相关文章 9

Metrics

本文评价

推荐阅读 10