Li Yafei, Xie Zhiyong, Chen Lei, Yan Jianjun, Ma Yao, Wang Liansheng, Chen Zhong
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Gu Lou Area, Nanjing, 210029, China.
Department of Cardiology, Xuzhou Medical University, NO.209 Tongshan Road, Xuzhou, 221000, China.
BMC Cardiovasc Disord. 2017 Feb 10;17(1):57. doi: 10.1186/s12872-017-0489-2.
Early B-cell factor 1 (EBF1) is a transcription factor expressed primarily during early B cell development. Previous studies have shown EBF1 regulates blood glucose and lipid metabolism in mice with diabetes and central adiposity. Recently, a genetic variation (rs36071027) located in an EBF1 gene intron was associated with carotid artery intima-media thickness. However, whether this polymorphism is actually linked with coronary artery disease (CAD) and its severity remains unclear.
This study includes 293 CAD cases and 262 controls without CAD. All participants were devided into two groups based on their coronary angiography results. A polymerase chain reaction-ligase detection reaction was used to identify genotypes at rs36071027, and CAD patients were further divided into subgroups with one-, two-, or three-vessel stenosis reflective of CAD severity.
The frequency of the rs36071027 TT genotype was significantly higher in CAD cases versus controls (4.8% vs. 1.5%, 95% CI: 1.13-10.81 P = 0.029). Subjects with a variant genotype T allele had an increased risk of CAD compared to C allele carriers (additive model: 95% CI: 1.13-2.23, P = 0.008). After adjustment for cardiovascular risk factors, analysis of the additive and dominant models involving rs36071027 also revealed that T allele carriers had a significantly higher risk for CAD than C allele carriers (additive model: OR 1.56, 95% CI 1.10-2.22, P = 0.013; dominant model: OR 1.60, 95% CI 1.07-2.41, P = 0.023). Furthermore, both diabetes and the CT + TT rs36071027 genotype were significantly associated with three-vessel stenosis.
Our results in a Chinese population suggest that the TT genotype and T alleles in rs36071027 in the EBF1 gene are associated with an increased risk of CAD and its severity.
早期B细胞因子1（EBF1）是一种主要在早期B细胞发育过程中表达的转录因子。先前的研究表明，EBF1可调节患有糖尿病和中心性肥胖的小鼠的血糖和脂质代谢。最近，位于EBF1基因内含子中的一个基因变异（rs36071027）与颈动脉内膜中层厚度相关。然而，这种多态性是否真的与冠状动脉疾病（CAD）及其严重程度有关仍不清楚。
本研究纳入了293例CAD患者和262例无CAD的对照。所有参与者根据冠状动脉造影结果分为两组。采用聚合酶链反应-连接酶检测反应来确定rs36071027的基因型，CAD患者进一步分为反映CAD严重程度的单支、双支或三支血管狭窄亚组。
CAD患者中rs36071027 TT基因型的频率显著高于对照组（4.8%对1.5%，95%置信区间：1.13 - 10.81，P = 0.029）。与C等位基因携带者相比，具有变异基因型T等位基因的受试者患CAD的风险增加（相加模型：95%置信区间：1.13 - 2.23，P = 0.008）。在调整心血管危险因素后，对涉及rs36071027的相加和显性模型的分析还显示，T等位基因携带者患CAD的风险显著高于C等位基因携带者（相加模型：比值比1.56，95%置信区间1.10 - 2.22，P = 0.013；显性模型：比值比1.60，95%置信区间1.07 - 2.41，P = 0.023）。此外，糖尿病和CT + TT rs36071027基因型均与三支血管狭窄显著相关。
我们在中国人群中的研究结果表明，EBF1基因中rs36071027的TT基因型和T等位基因与CAD风险增加及其严重程度相关。
