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Lancet:遗传引起的血浆HDL胆固醇升高与心肌梗塞风险无关

2012-08-17 SHUMUFENG 丁香园

       LIPG Asn396Ser多态现象携带者与非携带者血浆HDL胆固醇含量 高血浆HDL胆固醇含量与心肌梗塞风险降低相关,但其间的因果关系还存在争议。既往研究已知基因型由减数分裂随机决定,独立于非遗传混杂因素,并且不随疾病进展而改变,美国哈佛大学人类基因与心血管研究中心Sekar Kathiresan博士的这一研究旨在探索孟

       LIPG Asn396Ser多态现象携带者与非携带者血浆HDL胆固醇含量

高血浆HDL胆固醇含量与心肌梗塞风险降低相关,但其间的因果关系还存在争议。既往研究已知基因型由减数分裂随机决定,独立于非遗传混杂因素,并且不随疾病进展而改变,美国哈佛大学人类基因与心血管研究中心Sekar Kathiresan博士的这一研究旨在探索孟德尔定律用于检测血浆生物标记物与疾病之间因果关系的假设是否正确。他们发现一些可升高血浆HDL胆固醇水平的遗传机制似乎不能降低心肌梗塞风险。相关论文发表于国际权威杂志Lancet 2012年8月9日在线版。

研究人员进行了两项孟德尔随机化分析。第一项,随机人员借助仪器设备对内皮脂肪酶基因(LIPG Asn396Ser)单核苷酸多态性(SNP)进行分析,并在20项不同研究中检测了这一SNP位点(20 913例心肌梗塞患者,95 407例对照)。第二项,研究人员借助仪器对14项仅与HDL胆固醇相关的SNPs进行综合分析评分,评分对象为12 482例心肌梗塞患者和41 331例对照人群。作为阳性对照,研究人员同样对仅与LDL胆固醇相关的13个SNPs位点进行综合遗传评分。

结果显示,LIPG 396Ser等位基因携带者(2.6%出现率)与非携带者人群相比,前者拥有更高的HDL胆固醇水平(高出0·14 mmol/L, p=8×10−13),但两组间其他脂质指标和心肌梗塞相关非脂质风险因素相似。研究人员认为HDL胆固醇水平的差异导致了心肌梗塞风险水平相差了13% (优势比[OR] 0·87, 95% CI 0·84—0·91)。然而,研究人员注意到396Ser等位基因的存在与心肌梗塞风险无关OR 0·99, 95% CI 0·88—1·11, p=0·85)。从观察到的流行病学结果来看,HDL胆固醇水平每增加1 SD都会引起心肌梗塞风险的相应增加(OR 0·62, 95% CI 0·58—0·66)。然而,研究人员认为,因基因分析得分不同而引起的HDL胆固醇水平每增加1 SD,与心肌梗塞风险水平无关(OR 0·93, 95% CI 0·68—1·26, p=0·63)。对于LDL胆固醇,研究人员发现,对来源于流行病学观察结果(LDL胆固醇水平每增加1 SD会引起OR 1·54, 95% CI 1·45—1·63)的分析与来源于遗传得分的一致(OR 2·13, 95% CI 1·69—2·69, p=2×10−10)。

研究人员由此得出结论,一些可升高血浆HDL胆固醇水平的遗传机制似乎不能降低心肌梗塞风险。本研究结果对血浆HDL胆固醇水平升高会无一例外地引起心肌梗塞风险下降的假设提出了质疑。

PDF下载:Plasma HDL cholesterol and risk of myocardial infarction a mendelian randomisation study.pdf

链接:

Voight BF, Peloso GM, Orho-Melander M, Frikke-Schmidt R, Barbalic M, Jensen MK, Hindy G, Hólm H, Ding EL, Johnson T, Schunkert H, Samani NJ, Clarke R, Hopewell JC, Thompson JF, Li M, Thorleifsson G, Newton-Cheh C, Musunuru K, Pirruccello JP, Saleheen D, Chen L, Stewart A, Schillert A, Thorsteinsdottir U, Thorgeirsson G, Anand S, Engert JC, Morgan T, Spertus J, Stoll M, Berger K, Martinelli N, Girelli D, McKeown PP, Patterson CC, Epstein SE, Devaney J, Burnett MS, Mooser V, Ripatti S, Surakka I, Nieminen MS, Sinisalo J, Lokki ML, Perola M, Havulinna A, de Faire U, Gigante B, Ingelsson E, Zeller T, Wild P, de Bakker PI, Klungel OH, Maitland-van der Zee AH, Peters BJ, de Boer A, Grobbee DE, Kamphuisen PW, Deneer VH, Elbers CC, Onland-Moret NC, Hofker MH, Wijmenga C, Verschuren WM, Boer JM, van der Schouw YT, Rasheed A, Frossard P, Demissie S, Willer C, Do R, Ordovas JM, Abecasis GR, Boehnke M, Mohlke KL, Daly MJ, Guiducci C, Burtt NP, Surti A, Gonzalez E, Purcell S, Gabriel S, Marrugat J, Peden J, Erdmann J, Diemert P, Willenborg C, König IR, Fischer M, Hengstenberg C, Ziegler A, Buysschaert I, Lambrechts D, Van de Werf F, Fox KA, El Mokhtari NE, Rubin D, Schrezenmeir J, Schreiber S, Schäfer A, Danesh J, Blankenberg S, Roberts R, McPherson R, Watkins H, Hall AS, Overvad K, Rimm E, Boerwinkle E, Tybjaerg-Hansen A, Cupples LA, Reilly MP, Melander O, Mannucci PM, Ardissino D, Siscovick D, Elosua R, Stefansson K, O'Donnell CJ, Salomaa V, Rader DJ, Peltonen L, Schwartz SM, Altshuler D, Kathiresan S.Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study.Lancet. 2012 Aug 11;380(9841):572-80.
 

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    2013-04-01 howi
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    2012-08-19 ZGMFX24A
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