Ye Zi, Austin Erin, Schaid Daniel J, Kullo Iftikhar J
Division of Cardiovascular Diseases and the Gonda Vascular Center, Mayo Clinic, Rochester, MN, USA.
Division of Cardiovascular Diseases and the Gonda Vascular Center, Mayo Clinic, Rochester, MN, USA; Department of Health Science Research, Mayo Clinic, Rochester, MN, USA.
Atherosclerosis. 2016 Mar;246:274-9. doi: 10.1016/j.atherosclerosis.2015.12.031. Epub 2016 Jan 5.
We investigated whether a multi-locus genetic risk scores (GRS) was associated with presence and progression of abdominal aortic aneurysm (AAA) in a case - control study.
The study comprised of 1124 patients with AAA (74 ± 8 years, 83% men, 52% of them with a maximal AAA size ≤ 5 cm) and 6524 non-cases (67 ± 11 years, 58% men) from the Mayo Vascular Disease Biorepository. AAA was defined as infrarenal abdominal aorta diameter ≥ 3.0 cm or history of AAA repair. Non-cases were participants without known AAA. A GRS was calculated using 4 SNPs associated with AAA at genome-wide significance (P ≤ 10(-8)). The GRS was associated with the presence of AAA after adjustment for age, sex, cardiovascular risk factors, atherosclerotic cardiovascular diseases and family history of aortic aneurysm: odds ratio (OR, 95% confidence interval, CI) 1.06 (1.04-1.09, p < 0.001). Adding GRS to conventional risk factors improved the association of presence of AAA (net reclassification index 14%, p < 0.001). In a subset of patients with AAA who had ≥ 2 imaging studies (n = 651, mean (SE) growth rate 2.47 (0.11) mm/year during a mean time interval of 5.41 years), GRS, baseline size, diabetes and family history were each associated with aneurysm growth rate in univariate association (all p < 0.05). The estimated mean aneurysm growth rate was 0.50 mm/year higher in those with GRS > median (5.78) than those with GRS ≤ median (p = 0.01), after adjustment for baseline size (p < 0.001), diabetes (p = 0.046) and family history of aortic aneurysm (p = 0.02).
A multi-locus GRS was associated with presence of AAA and greater aneurysm expansion.
在一项病例对照研究中，我们调查了多基因座遗传风险评分（GRS）是否与腹主动脉瘤（AAA）的发生及进展相关。
该研究纳入了梅奥血管疾病生物样本库中的1124例AAA患者（74±8岁，83%为男性，其中52%的AAA最大直径≤5 cm）和6524例非病例（67±11岁，58%为男性）。AAA定义为肾下腹主动脉直径≥3.0 cm或有AAA修复史。非病例为无已知AAA的参与者。使用4个在全基因组水平具有显著意义（P≤10⁻⁸）的与AAA相关的单核苷酸多态性（SNP）计算GRS。在调整年龄、性别、心血管危险因素、动脉粥样硬化性心血管疾病和主动脉瘤家族史后，GRS与AAA的发生相关：比值比（OR，95%置信区间，CI）为1.06（1.04 - 1.09，p<0.001）。将GRS添加到传统危险因素中可改善AAA存在情况的关联性（净重新分类指数为14%，p<0.001）。在一组有≥2次影像学检查的AAA患者亚组（n = 651，在平均时间间隔5.41年期间平均（标准误）生长速率为2.47（0.11）mm/年）中，GRS、基线大小、糖尿病和家族史在单变量关联中均与动脉瘤生长速率相关（所有p<0.05）。在调整基线大小（p<0.001）、糖尿病（p = 0.046）和主动脉瘤家族史（p = 0.02）后，GRS>中位数（5.78）者的估计平均动脉瘤生长速率比GRS≤中位数者高0.50 mm/年（p = 0.01）。
多基因座GRS与AAA的存在及更大的动脉瘤扩张相关。
