The influence of metabolic syndrome, physical activity and genotype on catechol-O-methyl transferase promoter-region methylation in schizophrenia.
The influence of metabolic syndrome, physical activity and genotype on catechol-O-methyl transferase promoter-region methylation in schizophrenia.
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DOI：
10.1038/tpj.2012.6
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发表时间：
2013-06
期刊：
影响因子：
--
通讯作者：
Ellingrod VL
中科院分区：
文献类型：
--
作者：
Lott SA;Burghardt PR;Burghardt KJ;Bly MJ;Grove TB;Ellingrod VL
儿茶酚-O-甲基转移酶（COMT）158 Val/Met变体已被认为在COMT功能中发挥作用。COMT的表观遗传调控可能进一步影响这些患者人群中代谢综合征的患病率。本研究旨在探讨接受非典型抗精神病药物（AAP）治疗的精神分裂症患者中COMT启动子甲基化与代谢综合征的相关性。从筛选代谢综合征的精神分裂症受试者的外周血样本中提取DNA。焦磷酸测序用于分析COMT-s启动子区域的两个甲基化位点。分析AAP使用、生活方式变量、代谢综合征和COMT基因型与峰值甲基化值之间的关系。报告了85例受试者的数据。CpG位点1的甲基化平均值为79.08%（± 4.71），位点2的甲基化平均值为12.43%（±1.19）。COMT基因型被证明是位点1（F（2，84）= 5.78，p=0.0044）和位点2（F（2，84），p=0.027）上COMT甲基化状态的指标。在瓦尔/瓦尔纯合子患者中发现体力活动与COMT启动子区域甲基化之间存在显著负相关（位点1：p=0.013和位点2：p=0.019）。Met/Met纯合子显示启动子位点甲基化与体力活动呈正相关（位点1：p=0.027，位点2：p=0.005），CpG位点甲基化与代谢综合征呈正相关（位点1：p=0.002;位点2：p=0.001）。这项研究的结果表明，COMT启动子区甲基化在很大程度上受到COMT基因型的影响，体力活动在COMT的表观遗传调节中起着重要作用。
The catechol-o-methyl transferase (COMT) 158Val/Met variant has been suggested to play a role in COMT function. Epigenetic regulation of COMT may further influence the prevalence of metabolic syndrome in these patient populations. This study examined the correlation between COMT promoter methylation and metabolic syndrome in schizophrenia patients receiving atypical antipsychotic (AAP) therapy. DNA was extracted from peripheral blood samples of schizophrenia subjects screened for metabolic syndrome. Pyrosequencing was used to analyze two methylation sites of the COMT-s promoter region. Associations between AAP use, lifestyle variables, metabolic syndrome, and COMT genotype with peak methylation values were analyzed. Data are reported in 85 subjects. Methylation on CpG site 1 had a mean of 79.08% (± 4.71) and 12.43% (±1.19) on site 2. COMT genotype proved to be an indicator of COMT methylation status on site 1 (F(2,84) = 5.78, p=0.0044) and site 2 (F(2,84), p=0.027). A significant negative correlation between physical activity and COMT promoter region methylation was found in Val/Val homozygous patients (Site 1: p=0.013 and Site 2: p=0.019). Those homozygous for Met/Met showed a positive correlation between promoter site methylation and physical activity (Site 1: p=0.027, Site 2: p=0.005), and between CpG site methylation and metabolic syndrome (Site 1: p=0.002; Site 2: p=0.001). The results of this study suggest COMT promoter region methylation is largely influenced by COMT genotype and that physical activity plays a significant role in epigenetic modulation of COMT.
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DOI：
10.1097/hjr.0b013e3280ecfd56
发表时间：
2007-10-01
影响因子：
--
作者：
Orrell, Alison;Doherty, Patrick;Lewin, Robert
通讯作者：
Lewin, Robert
影响因子：
3.5
作者：
Dempster EL;Pidsley R;Schalkwyk LC;Owens S;Georgiades A;Kane F;Kalidindi S;Picchioni M;Kravariti E;Toulopoulou T;Murray RM;Mill J
通讯作者：
Mill J
影响因子：
4.5
作者：
Nieratschker, Vanessa;Frank, Josef;Schulze, Thomas G.
通讯作者：
Schulze, Thomas G.
影响因子：
4.5
作者：
Ellingrod, Vicki L.;Miller, Del D.;Kerr, Jane
通讯作者：
Kerr, Jane
影响因子：
10.6
作者：
Bruder, GE;Keilp, JG;Gilliam, TC
通讯作者：
Gilliam, TC