Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital, Guangxi Medical University, 22 Shuangyong Road, Nanning, 530021, Guangxi, People's Republic of China.
Department of Neurology, The First Affiliated Hospital, Guangxi Medical University, Nanning, 530021, Guangxi, People's Republic of China.
Lipids Health Dis. 2018 Feb 17;17(1):30. doi: 10.1186/s12944-018-0677-9.
Little is known about the association of the dedicator of cytokinesis 7 (DOCK7 rs1748195) and angiopoietin like 3 (ANGPTL3 rs12563308) single nucleotide polymorphisms (SNPs) and their haplotypes with serum lipid levels and the risk of coronary artery disease (CAD) and ischemic stroke (IS) in the Chinese populations. This study aimed to detect such association in a Southern Chinese Han population.
This study included 1728 subjects (CAD, 568; IS, 539; and controls, 621). Genotypes of the two SNPs were determined by the Snapshot technology.
The genotypic and allelic frequencies of the rs1748195 SNP were different between CAD patients and controls (P < 0.05 for each), the rs1748195G allele frequency was higher in CAD patients than in controls (27.6% vs. 23.6%, P = 0.024). The genotypic frequencies of the rs12563308 SNP were also different between CAD patients and controls (P = 0.021). The rs1748195 SNP was associated with an increased risk of CAD after controlling for potential confounders and Bonferroni correction (P < 0.025 considered statistically significant; Recessive: OR = 1.79, 95% CI = 1.04-3.06, P = 0.017; Log-additive: OR = 1.27, 95% CI = 1.02-1.57, P = 0.014), whereas the rs12563308 SNP was associated with a decreased risk of CAD (Dominant: OR = 0.69, 95% CI = 0.45-0.94, P = 0.011; Log-additive: OR = 0.73, 95% CI = 0.49-0.89, P = 0.009). The rs1748195 SNP was also associated with an increased risk of severity to coronary artery atherosclerosis (Dominant: OR = 1.45, 95% CI = 1.07-2.11, P = 0.017; Log-additive: OR = 1.35, 95% CI = 1.09-1.82, P = 0.013). The interactions of SNP-environment on serum lipid levels and the risk of severity to coronary artery atherosclerosis, CAD and IS were noted. The rs1748195G-rs12563308T haplotype was associated with an increased angiographic severity to coronary artery atherosclerosis (OR = 1.46, 95% CI = 1.05-2.03), and the risk of CAD (OR = 1.37, 95% CI = 1.08-1.74). The interactions of haplotype-hypertension on the risk of CAD and haplotype-drinking on the risk of CAD/IS were observed.
These results suggest that the DOCK-ANGPTL3 SNPs and their haplotypes were associated with the angiographic severity to coronary artery atherosclerosis and the risk of CAD and IS in the Southern Chinese Han population.
关于细胞分裂蛋白 7(DOCK7 rs1748195)和血管生成素样 3(ANGPTL3 rs12563308)单核苷酸多态性(SNP)及其单体型与血清脂质水平以及冠心病(CAD)和缺血性卒中(IS)风险的关联,人们知之甚少。本研究旨在检测中国南方汉族人群中是否存在这种关联。
本研究纳入了 1728 例受试者(CAD 患者 568 例,IS 患者 539 例,对照组 621 例)。采用 Snapshot 技术检测两个 SNP 的基因型。
rs1748195 位点的基因型和等位基因频率在 CAD 患者和对照组之间存在差异(每个 P 值均<0.05),CAD 患者的 rs1748195G 等位基因频率高于对照组(27.6%比 23.6%,P=0.024)。rs12563308 位点的基因型频率在 CAD 患者和对照组之间也存在差异(P=0.021)。在控制潜在混杂因素和 Bonferroni 校正后,rs1748195 SNP 与 CAD 风险增加相关(认为统计学显著的 P<0.025;隐性模型:OR=1.79,95%CI=1.04-3.06,P=0.017;对数加性模型:OR=1.27,95%CI=1.02-1.57,P=0.014),而 rs12563308 SNP 与 CAD 风险降低相关(显性模型:OR=0.69,95%CI=0.45-0.94,P=0.011;对数加性模型:OR=0.73,95%CI=0.49-0.89,P=0.009)。rs1748195 SNP 也与冠状动脉粥样硬化严重程度的风险增加相关(显性模型:OR=1.45,95%CI=1.07-2.11,P=0.017;对数加性模型:OR=1.35,95%CI=1.09-1.82,P=0.013)。还观察到 SNP-环境对血清脂质水平和冠状动脉粥样硬化严重程度、CAD 和 IS 风险的交互作用。rs1748195G-rs12563308T 单体型与冠状动脉粥样硬化严重程度(OR=1.46,95%CI=1.05-2.03)和 CAD 风险(OR=1.37,95%CI=1.08-1.74)相关。还观察到单体型-高血压对 CAD 风险的交互作用和单体型-饮酒对 CAD/IS 风险的交互作用。
这些结果表明,DOCK-ANGPTL3 SNP 及其单体型与中国南方汉族人群的冠状动脉粥样硬化严重程度以及 CAD 和 IS 风险相关。