Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115, USA.
Circulation. 2011 Feb 1;123(4):374-80. doi: 10.1161/CIRCULATIONAHA.110.976613. Epub 2011 Jan 17.
Genome-wide association studies have identified loci associated with coronary heart disease in whites of European ancestry. This study evaluated whether genetic markers previously identified in whites are associated with nonfatal acute myocardial infarction (MI) in Hispanics.
Cases (n=1989) with a first nonfatal acute MI and population-based controls (n=2096) living in Costa Rica were studied. Fourteen single-nucleotide polymorphisms were genotyped. Seven single-nucleotide polymorphisms at 3 independent loci showed significant associations with MI. The odds ratios for the loci with the strongest associations were 1.16 (95 confidence interval [CI], 1.05 to 1.27) for rs4977574 (CDKN2A/2B), 1.15 (95 CI, 1.03 to 1.29) for rs646776 (CELSR2-PSRC1-SORT1), and 1.22 (95 CI, 1.08 to 1.38) for rs501120 (CXCL12); the corresponding PARs were 6.8, 10.5, and 15.2; respectively. We developed a genetic risk score by summing the number of the top 3 associated risk alleles. The OR for MI per genetic risk score unit was 1.18 (95 CI, 1.11 to 1.25; P=4.83 × 10(-8)). Discrimination of MI was significantly improved (P=0.02) when the genetic risk score was added to a model including clinical predictors. However, the increase in the area under the receiver-operating characteristic curve after the genetic risk score was added was moderate, from 0.67 (95 CI, 0.65 to 0.69) to 0.68 (95 CI, 0.66 to 0.70).
These results indicate both the consistency and disparity of genetic effects on risk of MI between Hispanic and white populations. The improvement in the identified genetic markers on discrimination of MI in Hispanics was modest.
全基因组关联研究已经确定了与欧洲血统白人冠心病相关的基因座。本研究评估了先前在白人中确定的遗传标记是否与西班牙裔人群中的非致死性急性心肌梗死（MI）相关。
在哥斯达黎加居住的 1989 例首次非致死性急性 MI 病例和基于人群的 2096 例对照进行了研究。对 14 个单核苷酸多态性进行了基因分型。在 3 个独立的基因座中有 7 个单核苷酸多态性与 MI 显著相关。具有最强关联的基因座的比值比为 rs4977574（CDKN2A/2B）的 1.16（95%置信区间[CI]，1.05 至 1.27），rs646776（CELSR2-PSRC1-SORT1）的 1.15（95%CI，1.03 至 1.29）和 rs501120（CXCL12）的 1.22（95%CI，1.08 至 1.38）；相应的 PAR 分别为 6.8、10.5 和 15.2。通过将前 3 个相关风险等位基因的数量相加，我们构建了一个遗传风险评分。每单位遗传风险评分的 MI 比值比为 1.18（95%CI，1.11 至 1.25；P=4.83×10（-8））。当将遗传风险评分添加到包含临床预测因子的模型中时，MI 的区分明显改善（P=0.02）。然而，添加遗传风险评分后，接收者操作特征曲线下面积的增加适中，从 0.67（95%CI，0.65 至 0.69）增加到 0.68（95%CI，0.66 至 0.70）。
这些结果表明，遗传对西班牙裔和白人人群 MI 风险的影响既有一致性也有差异。在西班牙裔人群中，确定的遗传标记对 MI 区分的改善程度较小。
