载脂蛋白(a)蛋白酶样结构域的多态性与严重冠状动脉疾病相关。
A polymorphism in the protease-like domain of apolipoprotein(a) is associated with severe coronary artery disease.
作者信息
Luke May M, Kane John P, Liu Dongming M, Rowland Charles M, Shiffman Dov, Cassano June, Catanese Joseph J, Pullinger Clive R, Leong Diane U, Arellano Andre R, Tong Carmen H, Movsesyan Irina, Naya-Vigne Josephina, Noordhof Curtis, Feric Nicole T, Malloy Mary J, Topol Eric J, Koschinsky Marlys L, Devlin James J, Ellis Stephen G
机构信息
Celera, 1401 Harbor Bay Parkway, Alameda, CA 94502, USA.
出版信息
Arterioscler Thromb Vasc Biol. 2007 Sep;27(9):2030-6. doi: 10.1161/ATVBAHA.107.141291. Epub 2007 Jun 14.
OBJECTIVES
The purpose of this study was to identify genetic variants associated with severe coronary artery disease (CAD).
METHODS AND RESULTS
We used 3 case-control studies of white subjects whose severity of CAD was assessed by angiography. The first 2 studies were used to generate hypotheses that were then tested in the third study. We tested 12,077 putative functional single nucleotide polymorphisms (SNPs) in Study 1 (781 cases, 603 controls) and identified 302 SNPs nominally associated with severe CAD. Testing these 302 SNPs in Study 2 (471 cases, 298 controls), we found 5 (in LPA, CALM1, HAP1, AP3B1, and ABCG2) were nominally associated with severe CAD and had the same risk alleles in both studies. We then tested these 5 SNPs in Study 3 (554 cases, 373 controls). We found 1 SNP that was associated with severe CAD: LPA I4399M (rs3798220). LPA encodes apolipoprotein(a), a component of lipoprotein(a). I4399M is located in the protease-like domain of apolipoprotein(a). Compared with noncarriers, carriers of the 4399M risk allele (2.7% of controls) had an adjusted odds ratio for severe CAD of 3.14 (confidence interval 1.51 to 6.56), and had 5-fold higher median plasma lipoprotein(a) levels (P=0.003).
CONCLUSIONS
The LPA I4399M SNP is associated with severe CAD and plasma lipoprotein(a) levels.
目的
本研究旨在识别与严重冠状动脉疾病（CAD）相关的基因变异。
方法与结果
我们对白人受试者进行了3项病例对照研究，通过血管造影评估CAD的严重程度。前两项研究用于生成假设，然后在第三项研究中进行检验。我们在研究1（781例病例，603例对照）中检测了12,077个推定的功能性单核苷酸多态性（SNP），并鉴定出302个与严重CAD名义上相关的SNP。在研究2（471例病例，298例对照）中对这302个SNP进行检测，我们发现5个（位于LPA、CALM1、HAP1、AP3B1和ABCG2基因中）与严重CAD名义上相关，且在两项研究中具有相同的风险等位基因。然后我们在研究3（554例病例，373例对照）中对这5个SNP进行检测。我们发现1个与严重CAD相关的SNP：LPA I4399M（rs3798220）。LPA编码载脂蛋白(a)，它是脂蛋白(a)的一个组成部分。I4399M位于载脂蛋白(a)的蛋白酶样结构域。与非携带者相比，4399M风险等位基因的携带者（占对照的2.7%）发生严重CAD的校正比值比为3.14（置信区间1.51至6.56），且血浆脂蛋白(a)水平的中位数高5倍（P = 0.003）。
结论
LPA I4399M SNP与严重CAD及血浆脂蛋白(a)水平相关。
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