Methylation patterns of cell-free plasma DNA in relapsing-remitting multiple sclerosis.
Methylation patterns of cell-free plasma DNA in relapsing-remitting multiple sclerosis.
复制标题
DOI：
10.1016/j.jns.2009.12.018
复制
发表时间：
2010-03-15
影响因子：
4.4
通讯作者：
Levenson, Victor
中科院分区：
文献类型：
--
作者：
Liggett, Thomas;Melnikov, Anatoliy;Tilwalli, Shilpa;Yi, Qilong;Chen, Haiyan;Replogle, Charles;Feng, Xuan;Reder, Anthony;Stefoski, Dusan;Balabanov, Roumen;Levenson, Victor
人们对多发性硬化症(MS)生物标记物开发的新靶点越来越感兴趣。本研究的目的是比较复发-缓解型多发性硬化症(RRMS)患者和健康人血浆中游离细胞DNA(CfpDNA)的浓度和甲基化模式。检查了三个30名患者的队列：RRMS患者，无论是缓解还是恶化，以及作为对照的健康人。用标准荧光分光光度法测cfpDNA浓度。56个基因启动子的甲基化模式通过基于微阵列的分析(方法Det-56)来确定。对数据进行分析，以确定研究组之间的统计相关差异。RRMS患者的cfpDNA浓度是健康对照组的四到八倍。CfpDNA甲基化模式在三组比较中均有显著差异：缓解期RRMS患者与健康对照组的敏感度和特异度分别为79.2%和92.9%，急性加重期和缓解期RRMS患者的敏感度和特异度分别为75.9%和91.5%，70.8%和71.2%。根据我们的发现，我们得出结论，RRMS患者表现出独特的疾病和状态特异性的cfpDNA变化。我们的发现具有临床意义，因为它们可以用于开发潜在的MS新生物标记物。这是我们所知的第一个描述MS患者cfpDNA变化的报告。
There is growing interest for identification of new targets for biomarker development in multiple sclerosis (MS). The goal of this study was to compare the concentration and the methylation patterns of cell-free plasma DNA (cfpDNA) in patients with relapsing-remitting multiple sclerosis (RRMS) and healthy individuals. Three 30-patient cohorts were examined: patients with RRMS, in either remission or exacerbation, and healthy individuals as controls. Concentration of cfpDNA was determined using a standard fluorometric assay. Patterns of methylation in 56 gene promoters were determined by a microarray-based assay (MethDet-56). The data were analyzed to identify statistically relevant differences among the study groups. The concentration of cfpDNA in patients with RRMS was four to eight-fold higher compared to healthy controls. Significant differences in cfpDNA methylation patterns were detected in all three comparisons: RRMS patients in remission versus healthy controls were recognized with 79.2% sensitivity and 92.9% specificity; RRMS patients in exacerbation versus healthy controls were recognized with 75.9% sensitivity and 91.5% specificity; and RRMS patients in exacerbation versus those in remission were recognized with 70.8% sensitivity and 71.2% specificity. Based on our findings, we conclude that patients with RRMS display unique disease- and state-specific changes of cfpDNA. Our findings are of clinical significance as they could be used in development of potentially new biomarkers for MS. This is the first report in our knowledge describing such changes of cfpDNA in patients with MS.
登录
查看更多内容
影响因子：
4.5
作者：
Christensen BC;Houseman EA;Marsit CJ;Zheng S;Wrensch MR;Wiemels JL;Nelson HH;Karagas MR;Padbury JF;Bueno R;Sugarbaker DJ;Yeh RF;Wiencke JK;Kelsey KT
通讯作者：
Kelsey KT
影响因子：
6.7
作者：
Casaccia-Bonnefil, Patrizia;Pandozy, Gicivanna;Mastronardi, Fabrizio
通讯作者：
Mastronardi, Fabrizio
影响因子：
30.8
作者：
Gregory, Simon G.;Schmidt, Silke;Haines, Jonathan L.
通讯作者：
Haines, Jonathan L.
影响因子：
4.4
作者：
Gelman, AE;Zhang, JD;Turka, LA
通讯作者：
Turka, LA
影响因子：
--
作者：
Brentano, F;Schorr, O;Kyburz, D
通讯作者：
Kyburz, D