Circadian clock period inversely correlates with illness severity in cells from patients with alcohol use disorders.
Circadian clock period inversely correlates with illness severity in cells from patients with alcohol use disorders.
复制标题
昼夜节律时钟期与酒精使用障碍患者细胞的疾病严重程度成反比。
DOI：
10.1111/acer.12106
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发表时间：
2013-08
期刊：
影响因子：
--
通讯作者：
Welsh DK
中科院分区：
文献类型：
--
作者：
McCarthy MJ;Fernandes M;Kranzler HR;Covault JM;Welsh DK
临床和遗传学研究表明，生物钟基因可能有助于酒精使用障碍（AUD）的生物学机制。特别是，Per2基因调节突变动物的酒精消耗，在患有AUD的人类中，PER2中的10870变体与酒精消耗有关。然而，就功能而言，AUD患者的分子钟在很大程度上仍未表征。在皮肤成纤维细胞培养物中，从良好表征的人AUD患者（n=19）和对照组（n=13），我们使用了生物发光报告基因（Per2 β luc），以高采样密度测量基因表达的昼夜节律，持续5天。针对PER 2 10870变体对细胞进行基因分型。然后使用病例对照设计，并通过AUD受试者的遗传和临床特征分析节律参数周期和振幅。AUD病例和对照组之间的节律参数无差异。然而，时间与疾病严重程度（定义为满足酒精依赖标准的数量）呈负相关。PER 2变体10870与节律参数的差异无关。我们的数据表明，细胞生物钟的差异并不明显，在成纤维细胞从AUD案件和控制。然而，我们发现的证据表明，生物钟可能与AUD的轨迹改变有关，可能与疾病的严重程度有关。未来的工作将需要确定这种关联的机制基础。
Clinical and genetic studies suggest circadian clock genes may contribute to biological mechanisms underlying alcohol use disorders (AUD). In particular, the Per2 gene regulates alcohol consumption in mutant animals, and in humans with AUD, the 10870 variant in PER2 has been associated with alcohol consumption. However, with respect to function, the molecular clock remains largely uncharacterized in AUD patients. In skin fibroblast cultures from well-characterized human AUD patients (n=19) and controls (n=13), we used a bioluminescent reporter gene (Per2∷luc) to measure circadian rhythms in gene expression at high sampling density for five days. Cells were genotyped for the PER2 10870 variant. The rhythm parameters period and amplitude were then analyzed using a case-control design, and by genetic and clinical characteristics of the AUD subjects. There were no differences between AUD cases and controls in rhythm parameters. However, period was inversely correlated with illness severity (defined as the number of alcohol dependence criteria met). The PER2 variant 10870 was not associated with differences in rhythm parameters. Our data suggest that differences in the cellular circadian clock are not pronounced in fibroblasts from AUD cases and controls. However, we found evidence that the circadian clock may be associated with an altered trajectory of AUD, possibly related to illness severity. Future work will be required to determine the mechanistic basis of this association.
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影响因子：
3.7
作者：
Pagani L;Semenova EA;Moriggi E;Revell VL;Hack LM;Lockley SW;Arendt J;Skene DJ;Meier F;Izakovic J;Wirz-Justice A;Cajochen C;Sergeeva OJ;Cheresiz SV;Danilenko KV;Eckert A;Brown SA
通讯作者：
Brown SA
影响因子：
3.4
作者：
Comasco E;Nordquist N;Göktürk C;Aslund C;Hallman J;Oreland L;Nilsson KW
通讯作者：
Nilsson KW
DOI：
10.1073/pnas.0707772105
发表时间：
2008-02-05
影响因子：
11.1
作者：
Brown, Steven A.;Kunz, Dieter;Kramer, Achim
通讯作者：
Kramer, Achim
影响因子：
2.8
作者：
Kovanen, Leena;Saarikoski, Sirkku T.;Partonen, Timo
通讯作者：
Partonen, Timo
酒精依赖性与ADH基因簇中的变体之间的全基因组显着关联。
影响因子：
3.4
作者：
Frank J;Cichon S;Treutlein J;Ridinger M;Mattheisen M;Hoffmann P;Herms S;Wodarz N;Soyka M;Zill P;Maier W;Mössner R;Gaebel W;Dahmen N;Scherbaum N;Schmäl C;Steffens M;Lucae S;Ising M;Müller-Myhsok B;Nöthen MM;Mann K;Kiefer F;Rietschel M
通讯作者：
Rietschel M