CRP polymorphisms and DNA methylation of the AIM2 gene influence associations between trauma exposure, PTSD, and C-reactive protein.
CRP polymorphisms and DNA methylation of the AIM2 gene influence associations between trauma exposure, PTSD, and C-reactive protein.
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DOI：
10.1016/j.bbi.2017.08.022
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发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
McGlinchey R
中科院分区：
文献类型：
--
作者：
Miller MW;Maniates H;Wolf EJ;Logue MW;Schichman SA;Stone A;Milberg W;McGlinchey R
最近的研究表明，创伤后应激障碍（PTSD）的病理生理学炎症过程。C-反应蛋白（CRP）是一种广泛使用的外周炎症指标，但对影响PTSD患者血液中C-反应蛋白（CRP）水平的遗传和表观遗传因素知之甚少。参与者是286名9/11冲突后的美国退伍军人（57%患有PTSD）。分析的重点是CRP基因的单核苷酸多态性（SNP）和AIM 2中cg 10636246的DNA甲基化-最近通过大规模表观基因组关联研究的结果与CRP水平相关的基因座。PTSD与血清CRP水平呈正相关，与未诊断为PTSD的患者相比，PTSD患者的CRP水平更可能处于临床升高范围。控制白色血细胞比例、遗传主成分、年龄和性别的多变量分析显示，这种关联是由AIM 2基因座的甲基化介导的。rs3091244是CRP启动子区的一个功能性SNP，它调节了终生创伤暴露与当前PTSD严重程度之间的关联。分析还显示，迄今为止进行的最大的CRP全基因组关联研究（rs 1205和rs 2794520）中的顶级SNP与PTSD显着相互作用，影响CRP水平。这些发现为PTSD病理生理学中炎症过程的遗传和表观遗传机制提供了新的见解，并为PTSD患者的生物标志物鉴定和治疗开发指明了新的方向。
Recent studies have implicated inflammatory processes in the pathophysiology of posttraumatic stress disorder (PTSD). C-reactive protein (CRP) is a widely-used measure of peripheral inflammation, but little is known about the genetic and epigenetic factors that influence blood levels of C-reactive protein (CRP) in individuals with PTSD. Participants were 286 U.S. military veterans of post-9/11 conflicts (57% with current PTSD). Analyses focused on single nucleotide polymorphisms (SNPs) in the CRP gene and DNA methylation at cg10636246 in AIM2—a locus recently linked to CRP levels through results from a large-scale epigenome-wide association study. PTSD was positively correlated with serum CRP levels with PTSD cases more likely to have CRP levels in the clinically-elevated range compared to those without a PTSD diagnosis. Multivariate analyses that controlled for white blood cell proportions, genetic principal components, age and sex, showed this association to be mediated by methylation at the AIM2 locus. rs3091244, a functional SNP in the CRP promoter region, moderated the association between lifetime trauma exposure and current PTSD severity. Analyses also revealed that the top SNPs from the largest genome-wide association study of CRP conducted to date (rs1205 and rs2794520) significantly interacted with PTSD to influence CRP levels. These findings provide new insights into genetic and epigenetic mechanisms of inflammatory processes in the pathophysiology of PTSD and point to new directions for biomarker identification and treatment development for patients with PTSD.
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DOI：
10.1080/10705519909540118
发表时间：
1999-01-01
影响因子：
6
作者：
Hu, Li-tze;Bentler, Peter M.
通讯作者：
Bentler, Peter M.
来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
37.8
作者：
Dehghan A;Dupuis J;Barbalic M;Bis JC;Eiriksdottir G;Lu C;Pellikka N;Wallaschofski H;Kettunen J;Henneman P;Baumert J;Strachan DP;Fuchsberger C;Vitart V;Wilson JF;Paré G;Naitza S;Rudock ME;Surakka I;de Geus EJ;Alizadeh BZ;Guralnik J;Shuldiner A;Tanaka T;Zee RY;Schnabel RB;Nambi V;Kavousi M;Ripatti S;Nauck M;Smith NL;Smith AV;Sundvall J;Scheet P;Liu Y;Ruokonen A;Rose LM;Larson MG;Hoogeveen RC;Freimer NB;Teumer A;Tracy RP;Launer LJ;Buring JE;Yamamoto JF;Folsom AR;Sijbrands EJ;Pankow J;Elliott P;Keaney JF;Sun W;Sarin AP;Fontes JD;Badola S;Astor BC;Hofman A;Pouta A;Werdan K;Greiser KH;Kuss O;Meyer zu Schwabedissen HE;Thiery J;Jamshidi Y;Nolte IM;Soranzo N;Spector TD;Völzke H;Parker AN;Aspelund T;Bates D;Young L;Tsui K;Siscovick DS;Guo X;Rotter JI;Uda M;Schlessinger D;Rudan I;Hicks AA;Penninx BW;Thorand B;Gieger C;Coresh J;Willemsen G;Harris TB;Uitterlinden AG;Järvelin MR;Rice K;Radke D;Salomaa V;Willems van Dijk K;Boerwinkle E;Vasan RS;Ferrucci L;Gibson QD;Bandinelli S;Snieder H;Boomsma DI;Xiao X;Campbell H;Hayward C;Pramstaller PP;van Duijn CM;Peltonen L;Psaty BM;Gudnason V;Ridker PM;Homuth G;Koenig W;Ballantyne CM;Witteman JC;Benjamin EJ;Perola M;Chasman DI
通讯作者：
Chasman DI
影响因子：
12.3
作者：
Jaffe AE;Irizarry RA
通讯作者：
Irizarry RA
影响因子：
6.8
作者：
Ancelin ML;Farré A;Carrière I;Ritchie K;Chaudieu I;Ryan J
通讯作者：
Ryan J