Department of Microbiology and Molecular Genetics, University of the Punjab, Lahore, Pakistan.
Center for Cardiovascular Genetics, British Heart Foundation Laboratories, University College London, London, UK.
Lipids Health Dis. 2018 Apr 19;17(1):89. doi: 10.1186/s12944-018-0736-2.
Coronary artery disease (CAD) remains the single most important cause of mortality worldwide. Many candidate and GWAS genetic variants have been identified in the recent years. In the current study, we selected six SNPs from various genes that have originally been identified in GWAS studies and examined the association of SNPs individually and as a genetic risk score (GRS) with CAD and blood lipid levels in the Pakistani subjects.
Six hundred twenty-four (404 cases and 219 controls) subjects were genotyped for variants rs10757274 in CDKN2A gene, rs17465637 in MIA3 gene, rs7025486 in DAB2IP gene, rs17228212 in SMAD3 gene, rs981887 in MRAS gene and rs1746048 in CXCL12 gene, by TaqMan and KASPar allele discrimination techniques. Serum lipid parameters were measured using commercially available kits. Statistical analyses were done using SPSS version 22.
Individually, the single SNPs were not associated with CAD (p < 0.05). However, the combined GRS of 6 SNPs was significantly higher in cases than controls (4.89 ± 0.11 vs 4.58 ± 0.08, p = 0.024). Among blood lipids, GRS showed significant positive association with serum triglycerides levels (p = 0.022).
The GRS was quantitatively associated with CAD risk and showed association with serum triglycerides 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.
冠心病（CAD）仍然是全球最重要的死亡原因。近年来，已经发现了许多候选基因和全基因组关联研究（GWAS）遗传变异。在本研究中，我们从各种最初在 GWAS 研究中发现的基因中选择了 6 个 SNP，并单独检查了 SNP 以及遗传风险评分（GRS）与巴基斯坦受试者 CAD 和血脂水平的关联。
624 名（404 例病例和 219 名对照）受试者采用 TaqMan 和 KASPar 等位基因鉴别技术对 CDKN2A 基因中的 rs10757274 变异、MIA3 基因中的 rs17465637 变异、DAB2IP 基因中的 rs7025486 变异、SMAD3 基因中的 rs17228212 变异、MRAS 基因中的 rs981887 变异和 CXCL12 基因中的 rs1746048 变异进行基因分型。使用商业试剂盒测量血清脂质参数。使用 SPSS 版本 22 进行统计分析。
单独的 SNP 与 CAD 无关（p < 0.05）。然而，6 个 SNP 的组合 GRS 在病例中明显高于对照组（4.89 ± 0.11 对 4.58 ± 0.08，p = 0.024）。在血脂方面，GRS 与血清甘油三酯水平呈显著正相关（p = 0.022）。
GRS 与 CAD 风险呈定量相关，并与血清甘油三酯水平呈关联，表明这些变异的机制至少部分是通过在携带大量风险等位基因的受试者中产生致动脉粥样硬化的脂质谱来实现的。
