Shaw Stanley Y, Cheng Susan, Cupples L Adrienne, Larson Martin G, McCabe Elizabeth L, Ngwa Julius S, Wang Ying A, Martin Roderick P, Klein Rachael J, Hashmi Basma, Ajijola Olujimi A, Lau Evan, O'Donnell Christopher J, Vasan Ramachandran S, Cohen Kenneth S, Wang Thomas J
Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Circ Cardiovasc Genet. 2011 Jun;4(3):296-304. doi: 10.1161/CIRCGENETICS.110.958470. Epub 2011 Apr 14.
Several bone marrow-derived cell populations may have angiogenic activity, including cells termed endothelial progenitor cells. Decreased numbers of circulating angiogenic cell populations have been associated with increased cardiovascular risk. However, few data exist from large, unselected samples, and the genetic determinants of these traits are unclear.
We examined the clinical and genetic correlates of early-outgrowth colony-forming units (CFUs) in 1799 participants of the Framingham Heart Study (mean age, 66 years; 54% women). Among individuals without cardiovascular disease (n = 1612), CFU number was inversely related to advanced age (P = 0.004), female sex (P = 0.04), and triglycerides (P = 0.008) and positively related to hormone replacement (P = 0.008) and statin therapy (P = 0.027) in stepwise multivariable analyses. Overall, CFU number was inversely related to the Framingham risk score (P = 0.01) but not with prevalent cardiovascular disease. In genome-wide association analyses in the entire sample, polymorphisms were associated with CFUs at the MOSC1 locus (P = 3.3 × 10(-7)) and at the SLC22A3-LPAL2-LPA locus (P = 4.9 × 10(-7)), a previously replicated susceptibility locus for myocardial infarction. Furthermore, alleles at the SLC22A3-LPAL2-LPA locus that were associated with decreased CFUs were also related to increased risk of myocardial infarction (P = 1.1 × 10(-4)).
In a community-based sample, early-outgrowth CFUs are inversely associated with select cardiovascular risk factors. Furthermore, genetic variants at the SLC22A3-LPAL2-LPA locus are associated with both decreased CFUs and an increased risk of myocardial infarction. These findings are consistent with the hypothesis that decreased circulating angiogenic cell populations promote susceptibility to myocardial infarction.
几种骨髓来源的细胞群可能具有血管生成活性，包括所谓的内皮祖细胞。循环血管生成细胞群数量减少与心血管风险增加有关。然而，来自大型非选择性样本的数据很少，这些特征的遗传决定因素尚不清楚。
我们在1799名弗雷明汉心脏研究参与者（平均年龄66岁；54%为女性）中检查了早期生长集落形成单位（CFU）的临床和遗传相关性。在无心血管疾病的个体（n = 1612）中，在逐步多变量分析中，CFU数量与高龄（P = 0.004）、女性（P = 0.04）和甘油三酯（P = 0.008）呈负相关，与激素替代治疗（P = 0.008）和他汀类药物治疗（P = 0.027）呈正相关。总体而言，CFU数量与弗雷明汉风险评分呈负相关（P = 0.01），但与心血管疾病患病率无关。在整个样本的全基因组关联分析中，多态性与MOSC1基因座处的CFU相关（P = 3.3×10⁻⁷）以及与SLC22A3-LPAL2-LPA基因座相关（P = 4.9×10⁻⁷），后者是先前已复制的心肌梗死易感基因座。此外，SLC22A3-LPAL2-LPA基因座上与CFU减少相关的等位基因也与心肌梗死风险增加有关（P = 1.1×10⁻⁴）。
在基于社区的样本中，早期生长的CFU与特定心血管危险因素呈负相关。此外，SLC22A3-LPAL2-LPA基因座的遗传变异与CFU减少和心肌梗死风险增加均相关。这些发现与循环血管生成细胞群减少促进心肌梗死易感性的假设一致。
