The Association Between C-Reactive Protein and Postoperative Delirium Differs by Catechol-O-Methyltransferase Genotype.
The Association Between C-Reactive Protein and Postoperative Delirium Differs by Catechol-O-Methyltransferase Genotype.
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DOI：
10.1016/j.jagp.2018.09.007
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发表时间：
2019-01
期刊：
影响因子：
--
通讯作者：
Marcantonio ER
中科院分区：
文献类型：
--
作者：
Vasunilashorn SM;Ngo LH;Jones RN;Inouye SK;Hall KT;Gallagher J;Dillon ST;Xie Z;Libermann TA;Marcantonio ER
儿茶酚-O-甲基转移酶（COMT）是降解应激激素的关键酶，可能影响谵妄的易感性。具有COMT（rs 4680）瓦尔/瓦尔基因型的个体（称为“战士”）耐受神经精神障碍和认知下降的发作，而具有Met/Met和瓦尔/Met基因型的个体（“非战士”）更易受这些病症的影响。我们评估了COMT基因型是否改变了急性期反应物（应激标志物）C反应蛋白（CRP）和术后谵妄之间的既定联系。前瞻性队列。两个学术医疗中心。547例年龄≥70岁接受重大非心脏手术的患者。我们收集血液，提取DNA，并使用等位基因特异性PCR检测进行COMT基因分型，考虑战士与非战士。采用ELISA法在术后第2天（POD 2）测量的高血浆CRP定义为基于样本的最高四分位数（≥234.12 mg/L）。谵妄是确定使用混乱评估方法，通过验证图表审查增强。我们使用根据年龄、性别和手术类型调整的广义线性模型，按COMT基因型分层，以确定CRP与谵妄之间的关联是否因COMT而不同。COMT战士的患病率为26%，术后谵妄发生率为23%。在COMT战士中，高CRP与谵妄无关（相对危险度[RR] 1.0，95%可信区间[CI] 0.4-2.6）。相反，在非战士中，我们发现高CRP和谵妄的预期关系（RR 1.5，95%CI 1.1-2.2）。COMT战士可能会受到保护，防止与高POD 2 CRP相关的谵妄风险增加。随着进一步的确认，COMT基因型可能有助于针对性干预谵妄预防脆弱的非战士群体。
Catechol-O-methyltransferase (COMT), a key enzyme in degrading stress hormones, may influence susceptibility to delirium. Individuals with the COMT (rs4680) Val/Val genotype (designated “warriors”) withstand the onset of neuropsychiatric disorders and cognitive decline, while individuals with Met/Met and Val/Met genotypes (“non-warriors”) are more susceptible to these conditions. We evaluated whether COMT genotype modifies the established association between acute phase reactant (stress marker) C-reactive protein (CRP) and postoperative delirium. Prospective cohort. Two academic medical centers. 547 patients age ≥70 undergoing major non-cardiac surgery. We collected blood, extracted DNA, and performed COMT genotyping using allele specific PCR assays, considering warriors vs. non-warriors. High plasma CRP, measured on postoperative day 2 (POD2) using ELISA, was defined by the highest sample-based quartile (≥234.12 mg/L). Delirium was determined using the Confusion Assessment Method, augmented by a validated chart review. We used generalized linear models adjusted for age, sex, and surgery type, stratified by COMT genotype, to determine whether the association between CRP and delirium differs by COMT. Prevalence of COMT warriors was 26%, and postoperative delirium occurred in 23%. Among COMT warriors, high CRP was not associated with delirium (relative risk[RR] 1.0, 95% confidence interval[CI] 0.4–2.6). In contrast, among non-warriors, we found the expected relationship of high CRP and delirium (RR 1.5, 95% CI 1.1–2.2). COMT warriors may be protected against the increased risk of delirium associated with high POD2 CRP. With further confirmation, COMT genotype may help to target interventions for delirium prevention to the vulnerable non-warrior group.
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DOI：
10.1038/tpj.2016.53
发表时间：
2016-10
期刊：
The pharmacogenomics journal
影响因子：
--
作者：
Hall KT;Kossowsky J;Oberlander TF;Kaptchuk TJ;Saul JP;Wyller VB;Fagermoen E;Sulheim D;Gjerstad J;Winger A;Mukamal KJ
通讯作者：
Mukamal KJ
影响因子：
6.3
作者：
Vasunilashorn SM;Dillon ST;Inouye SK;Ngo LH;Fong TG;Jones RN;Travison TG;Schmitt EM;Alsop DC;Freedman SD;Arnold SE;Metzger ED;Libermann TA;Marcantonio ER
通讯作者：
Marcantonio ER
影响因子：
7
作者：
Ritchie, C. W.;Newman, T. H.;Sampson, E. L.
通讯作者：
Sampson, E. L.
影响因子：
1.5
作者：
Pol, Robert A.;van Leeuwen, Barbara L.;Zeebregts, Clark J.
通讯作者：
Zeebregts, Clark J.
影响因子：
6.3
作者：
Saczynski JS;Kosar CM;Xu G;Puelle MR;Schmitt E;Jones RN;Marcantonio ER;Wong B;Isaza I;Inouye SK
通讯作者：
Inouye SK