Molecular Genetics and Genomics Program, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Cardiovasc Diabetol. 2013 Jun 25;12:95. doi: 10.1186/1475-2840-12-95.
Patients with type 2 diabetes (T2D) are at elevated risk for cardiovascular disease (CVD) events and mortality. Recent studies have assessed the impact of genetic variants affecting high-density lipoprotein cholesterol (HDL) concentrations on CVD risk in the general population. This study examined the utility of HDL-associated single nucleotide polymorphisms (SNPs) for CVD risk prediction in European Americans with T2D enrolled in the Diabetes Heart Study (DHS).
Genetic risk scores (GRS) of HDL-associated SNPs were constructed and evaluated for potential associations with mortality and with coronary artery calcified atherosclerotic plaque (CAC), a measure of subclinical CVD strongly associated with CVD events and mortality. Two sets of SNPs were used to construct GRS; while all SNPs were selected primarily for their impacts on HDL, one set of SNPs had pleiotropic effects on other lipid parameters, while the other set lacked effects on low-density lipoprotein cholesterol (LDL) or triglyceride concentrations.
The GRS were specifically associated with HDL concentrations (4.90 × 10(-7) < p < 0.02) in models adjusted for age, sex, and body mass index (BMI), but were not associated with LDL or triglycerides. Cox proportional hazards regression analysis suggested the HDL-associated GRS had no impact on risk of CVD-mortality (0.48 < p < 0.99) in models adjusted for other known CVD risk factors. However, associations between several of the GRS and CAC were observed (3.85 × 10(-4) < p < 0.03) in models adjusted for other known CVD risk factors.
The GRS analyzed in this study provide a tool for assessment of HDL-associated SNPs and their impact on CVD risk in T2D. The observed associations between several of the GRS and CAC suggest a potential role for HDL-associated SNPs on subclinical CVD risk in patients with T2D.
2 型糖尿病（T2D）患者发生心血管疾病（CVD）事件和死亡的风险增加。最近的研究评估了影响高密度脂蛋白胆固醇（HDL）浓度的遗传变异对普通人群 CVD 风险的影响。本研究检测了在参加糖尿病心脏研究（DHS）的欧洲裔美国人中，与 HDL 相关的单核苷酸多态性（SNP）对 T2D 患者 CVD 风险预测的作用。
构建了与 HDL 相关的 SNP 的遗传风险评分（GRS），并评估了其与死亡率以及冠状动脉钙化粥样硬化斑块（CAC）的潜在关联，CAC 是一种与 CVD 事件和死亡率密切相关的亚临床 CVD 的衡量指标。使用两套 SNP 来构建 GRS；虽然所有 SNP 主要是因其对 HDL 的影响而被选择，但一套 SNP 对其他脂质参数具有多效性影响，而另一套 SNP 对 LDL 或甘油三酯浓度没有影响。
在调整年龄、性别和体重指数（BMI）的模型中，GRS 与 HDL 浓度具有特异性关联（4.90×10(-7) < p < 0.02），但与 LDL 或甘油三酯无关。Cox 比例风险回归分析表明，在调整其他已知 CVD 风险因素的模型中，与 HDL 相关的 GRS 对 CVD 死亡率风险没有影响（0.48 < p < 0.99）。然而，在调整其他已知 CVD 风险因素的模型中，观察到几个 GRS 与 CAC 之间存在关联（3.85×10(-4) < p < 0.03）。
本研究分析的 GRS 为评估与 HDL 相关的 SNP 及其对 T2D 患者 CVD 风险的影响提供了一种工具。在调整其他已知 CVD 风险因素的模型中，观察到几个 GRS 与 CAC 之间存在关联，提示与 HDL 相关的 SNP 可能对 T2D 患者的亚临床 CVD 风险有影响。
