Systematic review: genetic biomarkers associated with anti-TNF treatment response in inflammatory bowel diseases.
Systematic review: genetic biomarkers associated with anti-TNF treatment response in inflammatory bowel diseases.
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DOI：
10.1111/apt.13736
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发表时间：
2016-09
影响因子：
7.6
通讯作者：
Andersen V
中科院分区：
文献类型：
--
作者：
Bek S;Nielsen JV;Bojesen AB;Franke A;Bank S;Vogel U;Andersen V
个性化药物，包括用于治疗选择的生物标志物，可以为更有效的患者治疗提供新的算法。遗传变异可能会影响药物反应，遗传标记可以帮助为个体患者选择最佳治疗策略。从文献中确定与炎症性肠病（IBD）、克罗恩病（CD）和溃疡性结肠炎患者抗肿瘤坏死因子（TNF）治疗反应相关的多态性和候选基因。我们进行了PubMed文献检索，并检索了报告多态性与抗TNF治疗反应之间相关性的原始数据的研究，并进行了Meta分析。使用生物学反应标准（C反应蛋白水平降低），FCGR 3A的功能多态性与CD患者的抗TNF治疗反应显著相关。Meta分析显示，TLR 2的多态性（rs3804099，OR（95% CI）= 2.17（1.35-3.47）]，rs11938228 [OR = 0.64（0.43-0.96）]、TLR4（rs5030728）[OR = 3.18（1.63-6.21）]、TLR9（rs352139）[OR = 0.43（0.21-0.88）]、TNFRSF1A（rs4149570）[OR = 2.06（1.02-4.17）]、IFNG（rs2430561）[OR = 1.66（1.05-2.63）]，使用临床应答标准，IL 6（rs 10499563）[OR = 1.65（1.04-2.63）]和IL 1B（rs 4848306）[OR = 1.88（1.05-3.35）]与IBD患者的应答显著相关。在探索性分析中，通过结合五个遗传标记实现了0.96的阳性预测值。目前尚无可充分预测抗TNF应答的遗传标记物可用于临床。遗传标记具有不随时间变化的优点。因此，需要采用无假设方法，在大型、特征良好的队列中检测大量多态性，以确定具有较大效应量的遗传特征，这些遗传特征可用作临床治疗选择的生物标志物。
Personalised medicine, including biomarkers for treatment selection, may provide new algorithms for more effective treatment of patients. Genetic variation may impact drug response and genetic markers could help selecting the best treatment strategy for the individual patient. To identify polymorphisms and candidate genes from the literature that are associated with anti‐tumour necrosis factor (TNF) treatment response in patients with inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis. We performed a PubMed literature search and retrieved studies reporting original data on association between polymorphisms and anti‐TNF treatment response and conducted a meta‐analysis. A functional polymorphism in FCGR3A was significantly associated with anti‐TNF treatment response among CD patients using biological response criterion (decrease in C‐reactive protein, levels). Meta‐analyses showed that polymorphisms in TLR2 (rs3804099, OR (95% CI) = 2.17 (1.35–3.47)], rs11938228 [OR = 0.64 (0.43–0.96)], TLR4 (rs5030728) [OR = 3.18 (1.63–6.21)], TLR9 (rs352139) [OR = 0.43 (0.21–0.88)], TNFRSF1A (rs4149570) [OR = 2.06 (1.02–4.17)], IFNG (rs2430561) [OR = 1.66 (1.05–2.63)], IL6 (rs10499563) [OR = 1.65 (1.04–2.63)] and IL1B (rs4848306) [OR = 1.88 (1.05–3.35)] were significantly associated with response among IBD patients using clinical response criteria. A positive predictive value of 0.96 was achieved by combining five genetic markers in an explorative analysis. There are no genetic markers currently available which are adequately predictive of anti‐TNF response for use in the clinic. Genetic markers bear the advantage that they do not change over time. Therefore, hypothesis‐free approaches, testing a large number of polymorphisms in large, well‐characterised cohorts, are required in order to identify genetic profiles with larger effect sizes, which could be employed as biomarkers for treatment selection in clinical settings.
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克罗恩病和溃疡性结肠炎表型的遗传决定因素：遗传关联研究。
DOI：
10.1016/s0140-6736(15)00465-1
发表时间：
2016-01-09
期刊：
Lancet (London, England)
影响因子：
--
作者：
Cleynen I;Boucher G;Jostins L;Schumm LP;Zeissig S;Ahmad T;Andersen V;Andrews JM;Annese V;Brand S;Brant SR;Cho JH;Daly MJ;Dubinsky M;Duerr RH;Ferguson LR;Franke A;Gearry RB;Goyette P;Hakonarson H;Halfvarson J;Hov JR;Huang H;Kennedy NA;Kupcinskas L;Lawrance IC;Lee JC;Satsangi J;Schreiber S;Théâtre E;van der Meulen-de Jong AE;Weersma RK;Wilson DC;International Inflammatory Bowel Disease Genetics Consortium;Parkes M;Vermeire S;Rioux JD;Mansfield J;Silverberg MS;Radford-Smith G;McGovern DP;Barrett JC;Lees CW
通讯作者：
Lees CW
影响因子：
--
作者：
Andersen V;Ernst A;Christensen J;Østergaard M;Jacobsen BA;Tjønneland A;Krarup HB;Vogel U
通讯作者：
Vogel U
影响因子：
7.6
作者：
Hlavaty, T;Pierik, M;Vermeire, S
通讯作者：
Vermeire, S
影响因子：
8
作者：
Dignass, A.;Van Assche, G.;Travis, S. P. L.
通讯作者：
Travis, S. P. L.
影响因子：
2.1
作者：
Koder, Silvo;Repnik, Katja;Potocnik, Uros
通讯作者：
Potocnik, Uros