使用包含21个变异体的遗传风险评分对巴基斯坦受试者进行冠状动脉疾病的遗传风险分析。

Genetic risk analysis of coronary artery disease in Pakistani subjects using a genetic risk score of 21 variants.

作者信息

Shahid Saleem Ullah, Cooper Jackie A, Beaney Katherine E, Li Kawah, Rehman Abdul, Humphries Steve E

机构信息

Department of Microbiology and Molecular Genetics, University of the Punjab, Lahore, 54590, Pakistan.

出版信息

Atherosclerosis. 2017 Mar;258:1-7. doi: 10.1016/j.atherosclerosis.2017.01.024. Epub 2017 Jan 22.

DOI:10.1016/j.atherosclerosis.2017.01.024

PMID:28167353

Abstract

BACKGROUND AND AIMS

Conventional coronary artery disease (CAD) risk factors like age, gender, blood lipids, hypertension and smoking have been the basis of CAD risk prediction algorithms, but provide only modest discrimination. Genetic risk score (GRS) may provide improved discrimination over and above conventional risk factors. Here we analyzed the genetic risk of CAD in subjects from Pakistan, using a GRS of 21 variants in 18 genes and examined whether the GRS is associated with blood lipid levels.

METHODS

625 (405 cases and 220 controls) subjects were genotyped for variants, NOS3 rs1799983, SMAD3 rs17228212, APOB rs1042031, LPA rs3798220, LPA rs10455872, SORT1 rs646776, APOE rs429358, GLUL rs10911021, FTO rs9939609, MIA3 rs17465637, CDKN2Ars10757274, DAB2IP rs7025486, CXCL12 rs1746048, ACE rs4341, APOA5 rs662799, CETP rs708272, MRAS rs9818870, LPL rs328, LPL rs1801177, PCSK9 rs11591147 and APOE rs7412 by TaqMan and KASPar allele discrimination techniques.

RESULTS

Individually, the single SNPs were not associated with CAD except APOB rs1042031 and FTO rs993969 (p = 0.01 and 0.009 respectively). However, the combined GRS of 21 SNPs was significantly higher in cases than controls (19.37 ± 2.56 vs. 18.47 ± 2.45, p = 2.9 × 10), and compared to the bottom quintile, CAD risk in the top quintile of the GRS was 2.96 (95% CI 1.71-5.13). Atherogenic blood lipids showed significant positive association with GRS.

CONCLUSIONS

The GRS was quantitatively associated with CAD risk and showed association with blood lipid levels, suggesting that the mechanism of these variants is likely to be, in part at least, through creating an atherogenic lipid profile in subjects carrying high numbers of risk alleles.

摘要

背景与目的

传统的冠状动脉疾病（CAD）危险因素，如年龄、性别、血脂、高血压和吸烟，一直是CAD风险预测算法的基础，但只能提供有限的区分度。遗传风险评分（GRS）可能比传统危险因素提供更好的区分度。在此，我们使用18个基因中21个变异的GRS分析了来自巴基斯坦受试者的CAD遗传风险，并研究了GRS是否与血脂水平相关。

方法

采用TaqMan和KASPar等位基因鉴别技术，对625名受试者（405例病例和220例对照）的NOS3 rs1799983、SMAD3 rs17228212、APOB rs1042031、LPA rs3798220、LPA rs10455872、SORT1 rs646776、APOE rs429358、GLUL rs10911021、FTO rs9939609、MIA3 rs17465637、CDKN2A rs10757274、DAB2IP rs7025486、CXCL12 rs1746048、ACE rs4341、APOA5 rs662799、CETP rs708272、MRAS rs9818870、LPL rs328、LPL rs1801177、PCSK9 rs11591147和APOE rs7412等变异进行基因分型。

结果

单个单核苷酸多态性（SNP）中，除APOB rs1042031和FTO rs993969外，其他均与CAD无关（p值分别为0.01和0.009）。然而，21个SNP的联合GRS在病例组中显著高于对照组（19.37±2.56 vs. 18.47±2.45，p = 2.9×10⁻⁴），与最低五分位数相比，GRS最高五分位数的CAD风险为2.96（95%可信区间1.71 - 5.13）。致动脉粥样硬化血脂与GRS呈显著正相关。