Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies.
Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies.
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DOI：
10.1016/s0140-6736(10)60545-4
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发表时间：
2010-05-08
期刊：
影响因子：
168.9
通讯作者：
Wood, A. M.
中科院分区：
文献类型：
--
作者：
Sarwar, Nadeem;Sandhu, Manjinder S.;Ricketts, Sally L.;Butterworth, Adam S.;Di Angelantonio, Emanuele;Boelcholdt, S. Matthijs;Ouwehand, Willem;Watkins, Hugh;Samani, Nilesh J.;Saleheen, Danish;Lawlor, Debbie;Reilly, Muredach P.;Hingorani, Aroon D.;Talmud, Philippa J.;Danesh, John;Braund, P. S.;Hall, A. S.;Thompson, J.;Marz, W.;Sivapalaratnam, S.;Soranzo, N.;Trip, M.;Casas, J. P.;Ebrahim, S.;Arsenault, B. J.;Boekholdt, S. M.;Khaw, K. T.;Wareham, N. J.;Grallert, H.;Illig, T.;Humphries, S. E.;Rader, D. J.;He, J.;Clarke, R.;Hamsten, R.;Hopewell, J. C.;Frossard, P.;Deloukas, P.;Ye, S.;Simpson, J. A.;Onat, A.;Komurcu-Bayrak, E.;Martinelli, N.;Olivieri, O.;Girelli, D.;Kivimaki, M.;Kumari, M.;Aouizerat, B. E.;Baum, L.;Campos, H.;Chaaba, R.;Chen, B. S.;Cho, E. Y.;Evans, D.;Hill, J.;Hsu, L. A.;Hubacek, J. A.;Lai, C. Q.;Lee, J. H.;Klos, K.;Liu, H.;Masana, L.;Melegh, B.;Nabika, T.;Ribalta, J.;Ruiz-Narvaez, E.;Thomas, G. N.;Tomlinson, B.;Szalai, C.;Vaverkova, H.;Yamada, Y.;Yang, Y.;Tipping, R. W.;Ford, C. E.;Pressel, S. L.;Ballantyne, C.;Brautbar, A.;Knuiman, M.;Winchup, P. H.;Wannamethee, S. G.;Morris, R. W.;Kiechl, S.;Willeit, J.;Santer, P.;Mayr, A.;Wald, N.;Yarnell, J. W. G.;Gallacher, J.;Casiglia, E.;Tikhonoff, V.;Cushman, M.;Psaty, B. M.;Tracy, R. P.;Tybjaerg-Hansen, A.;Nordestgaard, B. G.;Benn, M.;Frikke-Schmidt, R.;Giampaoli, S.;Palmieri, L.;Panico, S.;Vanuzzo, D.;Pilotto, L.;Gomez de la Camara, A.;Gomez-Gerique, J. A.;Simons, L.;McCallum, J.;Friedlander, Y.;Fowkes, F. G. R.;Lee, A. J.;Taylor, J.;Guralnik, J. M.;Phillips, C. L.;Wallace, W. R.;Blazer, D. G.;Brenner, H.;Raum, E.;Mueller, H.;Rothenbacher, D.;Jansson, J. H.;Wennberg, P.;Nissinen, A.;Donfrancesco, C.;Salomaa, V.;Harald, K.;Pencina, M. J.;Vartiainen, E.;D'Agostino, R. B.;Vasan, R. S.;Bladbjerg, E. M.;Jorgensen, T.;Moller, L.;Jespersen, J.;Dankner, R.;Chetrit, A.;Lubin, F.;Bjoerkelund, C.;Lissner, L.;Bengtsson, C.;Cremer, P.;Nagel, D.;Rodriguez, B.;Dekker, J. M.;Nijpels, G.;Stehouwer, C. D. A.;Sato, S.;Iso, H.;Kitamura, A.;Noda, H.;Salonen, J. T.;Nyssoenen, K.;Tuimainen, T. -P.;Voutilainen, S.;Meade, T. W.;Cooper, J. A.;Kuller, L. H.;Grandits, G.;Gillum, R.;Mussolino, M.;Rimm, E.;Hankinson, S.;Manson, J. A. E.;Pai, J. K.;Bauer, K. A.;Naito, Y.;Amouyel, P.;Arveiler, D.;Evans, A.;Ferrieres, J.;Schulte, H.;Assmann, G.;Packard, C. J.;Sattar, N.;Westendorp, R. G.;Buckley, B. M.;Cantin, B.;Lamarche, B.;Despres, J. -P.;Dagenais, G. R.;Barrett-Connor, E.;Wingard, D. L.;Bettencourt, R.;Gudnason, V.;Aspelund, T.;Sigurdsson, G.;Thorsson, B.;Trevisan, M.;Tunstall-Pedoe, H.;Tavendale, R.;Lowe, G. D. O.;Woodward, M.;Howard, B. V.;Zhang, Y.;Best, L.;Umans, J.;Ben-Shlomo, Y.;Davey-Smith, G.;Njolstad, I.;Mathiesen, E. B.;Lochen, M. L.;Wilsgaard, T.;Ingelsson, E.;Lind, I.;Giedraitis, V.;Michaeelsson, K.;Brunner, E.;Shipley, M.;Ridker, P.;Buring, J.;Shepherd, J.;Cobbe, S. M.;Ford, I.;Robertson, M.;Marin Ibanez, A.;Feskens, E. J. M.;Kromhout, D.;Walker, M.;Watson, S.;Collins, R.;Kaptoge, S.;Perry, P. L.;Sarwar, N.;Thompson, A.;Thompson, S. G.;White, I. R.;Wood, A. M.
是否阿糖胞苷介导的途径与冠心病的因果关系尚不确定。我们研究了一种调节甘油三酯浓度的遗传变异，以帮助判断因果关系的可能性。我们评估了载脂蛋白A5（APOA 5）基因的− 1131 T>C（rs662799）启动子多态性与甘油三酯浓度、其他几个危险因素和冠心病风险的关系。我们比较了遗传性升高的甘油三酯浓度的疾病风险（20，842名冠心病患者，35，206名对照）与前瞻性研究中记录的循环甘油三酯浓度等效差异（302，430名无心血管疾病史的参与者）;在279万人年的风险期间，有12，785例冠心病事件）。 我们分析了1795名没有心血管疾病史的人的− 1131 T>C，这些人通过核磁共振光谱获得了脂蛋白浓度和直径的信息。-1131 T>C的次要等位基因频率为8%（95% CI 7-9）。− 1131 T>C与几种非脂质风险因素或LDL胆固醇无显著相关，与较低的HDL胆固醇适度相关（每个C等位基因的平均差异为3.5%[95% CI 2.6 - 4.6]; 0.053 mmol/L [0.039 - 0.068]），载脂蛋白AI较低载脂蛋白B水平较高（3.2%[1.3 - 5.1]; 0.027 g/L [0.011 - 0.043]）。相比之下，对于每个C等位基因遗传，平均甘油三酯浓度为16.0%（95% CI 12.9 - 18.7），或0.25 mmol/L（0.20 - 0.29），更高（p= 4.4 ×10−24）。每个C等位基因患冠心病的比值比为1.18（95%CI 1.11 - 1.26; p= 2.6 ×10−7），这与前瞻性研究中记录的甘油三酯浓度每升高16%的风险比1.10（95%CI 1.08 - 1.12）一致。− 1131 T>C与较高的VLDL颗粒浓度（每个C等位基因的平均差异为12.2 nmol/L [95% CI 7.7 - 16.7]; p= 9.3 ×10−8）和较小的HDL颗粒尺寸（0.14 nm [0.08 - 0.20]; p= 7.0 ×10−5）显著相关，这些因素可能介导甘油三酯的作用。这些数据与阿糖胞苷介导的途径和冠心病之间的因果关系是一致的。英国心脏基金会，英国医学研究理事会，诺华。
Whether triglyceride-mediated pathways are causally relevant to coronary heart disease is uncertain. We studied a genetic variant that regulates triglyceride concentration to help judge likelihood of causality. We assessed the −1131T>C (rs662799) promoter polymorphism of the apolipoprotein A5 (APOA5) gene in relation to triglyceride concentration, several other risk factors, and risk of coronary heart disease. We compared disease risk for genetically-raised triglyceride concentration (20 842 patients with coronary heart disease, 35 206 controls) with that recorded for equivalent differences in circulating triglyceride concentration in prospective studies (302 430 participants with no history of cardiovascular disease; 12 785 incident cases of coronary heart disease during 2·79 million person-years at risk). We analysed −1131T>C in 1795 people without a history of cardiovascular disease who had information about lipoprotein concentration and diameter obtained by nuclear magnetic resonance spectroscopy. The minor allele frequency of −1131T>C was 8% (95% CI 7–9). −1131T>C was not significantly associated with several non-lipid risk factors or LDL cholesterol, and it was modestly associated with lower HDL cholesterol (mean difference per C allele 3·5% [95% CI 2·6–4·6]; 0·053 mmol/L [0·039–0·068]), lower apolipoprotein AI (1·3% [0·3–2·3]; 0·023 g/L [0·005–0·041]), and higher apolipoprotein B (3·2% [1·3–5·1]; 0·027 g/L [0·011–0·043]). By contrast, for every C allele inherited, mean triglyceride concentration was 16·0% (95% CI 12·9–18·7), or 0·25 mmol/L (0·20–0·29), higher (p=4·4×10−24). The odds ratio for coronary heart disease was 1·18 (95% CI 1·11–1·26; p=2·6×10−7) per C allele, which was concordant with the hazard ratio of 1·10 (95% CI 1·08–1·12) per 16% higher triglyceride concentration recorded in prospective studies. −1131T>C was significantly associated with higher VLDL particle concentration (mean difference per C allele 12·2 nmol/L [95% CI 7·7–16·7]; p=9·3×10−8) and smaller HDL particle size (0·14 nm [0·08–0·20]; p=7·0×10−5), factors that could mediate the effects of triglyceride. These data are consistent with a causal association between triglyceride-mediated pathways and coronary heart disease. British Heart Foundation, UK Medical Research Council, Novartis.