Shiffman Dov, Rowland Charles M, Louie Judy Z, Luke May M, Bare Lance A, Bolonick Joel I, Young Bradford A, Catanese Joseph J, Stiggins Charles F, Pullinger Clive R, Topol Eric J, Malloy Mary J, Kane John P, Ellis Stephen G, Devlin James J
Celera Inc., 1401 Harbor Bay Pkwy, Alameda, California 94502, USA.
Arterioscler Thromb Vasc Biol. 2006 Jul;26(7):1613-8. doi: 10.1161/01.ATV.0000226543.77214.e4. Epub 2006 May 11.
Identify gene variants associated with early-onset myocardial infarction (MI).
We tested 11 647 single-nucleotide polymorphisms (SNPs) for association with early-onset MI in a case-control study (study 1 200 cases, 262 controls). To reduce the number of false positives among the 666 SNPs that were nominally associated with early-onset MI (P<0.05) in study 1, we tested these SNPs in study 2 (434 cases, 504 controls). We found that 8 of the 666 SNPs were associated with early-onset MI in study 2 (P<0.05) and had the same risk alleles as in study 1. These 8 SNPs were then tested for association with early-onset MI in study 3 (187 cases, 434 controls). We found that a VAMP8 variant (P = 0.025; odds ratio [OR], 1.75; CI, 1.17 to 2.62) and an HNRPUL1 variant (P = 0.0043; OR, 1.92; CI, 1.28 to 2.86) were associated with early-onset MI (nominal P<0.05; false discovery rate <10%) and had the same risk alleles in all 3 studies.
Variants in 2 genes were associated with early-onset MI: VAMP8, which is involved in platelet degranulation, and HNRPUL1, which encodes a ribonuclear protein. The identification of these variants could improve understanding of disease mechanisms and suggest novel drug targets.
鉴定与早发性心肌梗死（MI）相关的基因变异。
在一项病例对照研究中（研究1：200例病例，262例对照），我们检测了11647个单核苷酸多态性（SNP）与早发性MI的关联性。为减少研究1中名义上与早发性MI相关（P<0.05）的666个SNP中的假阳性数量，我们在研究2中（434例病例，504例对照）对这些SNP进行了检测。我们发现，666个SNP中的8个在研究2中与早发性MI相关（P<0.05），并且与研究1中的风险等位基因相同。然后在研究3中（187例病例，434例对照）对这8个SNP与早发性MI的关联性进行了检测。我们发现，一个VAMP8变异体（P = 0.025；比值比[OR]，1.75；可信区间[CI]，1.17至2.62）和一个HNRPUL1变异体（P = 0.0043；OR，1.92；CI，1.28至2.86）与早发性MI相关（名义P<0.05；错误发现率<10%），并且在所有3项研究中具有相同的风险等位基因。
2个基因中的变异体与早发性MI相关：参与血小板脱颗粒的VAMP8和编码核糖核蛋白的HNRPUL1。这些变异体的鉴定有助于增进对疾病机制的理解，并提示新的药物靶点。
