Sun Dandan, Wu Yupeng, Wang Honghu, Yan Hong, Liu Wen, Yang Jun
Department of Cardiovascular Ultrasound, The First Affiliated Hospital of China Medical University, Shenyang, China.
Department of Neurosurgery, The First Affiliated Hospital of China Medical University, Shenyang, China.
Oncotarget. 2017 Jan 10;8(2):2025-2033. doi: 10.18632/oncotarget.14014.
Toll-like receptor 4 (TLR4) is a key modulator in many inflammation-related diseases. Polymorphisms in the TLR4 gene may alter TLR4 expression and affect the extent and severity of coronary artery disease (CAD). We analyzed 3 polymorphisms of TLR4 in 607 Chinese subjects who underwent coronary arteriography. Blood samples were collected to identify the polymorphisms. We evaluated the relationships between the polymorphisms and the number of vessels involved in coronary stenosis, Gensini scores, and Duke prognostic scores. We found that rs11536889 was associated with an increased risk of 3-vessel disease. When subjects with 3-vessel disease were compared to subjects with nonsignificant CAD, rs11536889 variant genotypes were associated with an increased risk of 3-vessel disease (GC/CC vs. GG: OR=2.06, 95%CI=1.21-3.51). When subjects with 3-vessel disease were compared to subjects with 1-vessel disease, rs11536889 variant genotypes were associated with an increased risk of 3-vessel disease (GC vs. GG: OR=2.14, 95%CI=1.20-3.79; GC/CC vs. GG: OR=2.06, 95%CI=1.20-3.54). When subjects with 3-vessel disease were compared to subjects with non-3-vessel disease, rs11536889 variant genotypes were associated with an increased risk of 3-vessel disease (GC vs. GG: OR=1.76, 95%CI=1.12-2.75; GC/CC vs. GG: OR=1.83, 95%CI=1.19-2.82). The TLR4 rs11536889 polymorphism was also related to Gensini score (P=0.02). The Gensini score was higher in subjects with the variant CC and GC/CC genotype than in subjects with the wild GG genotype (61.28± 1.84 and 57.64±34.82 vs. 51.27±34.57). Our results demonstrate that TLR4 rs11536889 polymorphism is a novel genetic factor in the development of CAD, influencing the extent and severity of CAD.
Toll样受体4(TLR4)是许多炎症相关疾病的关键调节因子。TLR4基因多态性可能会改变TLR4表达,并影响冠状动脉疾病(CAD)的范围和严重程度。我们分析了607例接受冠状动脉造影的中国受试者的TLR4的3种多态性。采集血样以鉴定多态性。我们评估了多态性与冠状动脉狭窄累及血管数量、Gensini评分和杜克预后评分之间的关系。我们发现rs11536889与三支血管病变风险增加相关。当将三支血管病变受试者与无明显CAD的受试者进行比较时,rs11536889变异基因型与三支血管病变风险增加相关(GC/CC与GG相比:OR=2.06,95%CI=1.21-3.51)。当将三支血管病变受试者与单支血管病变受试者进行比较时,rs11536889变异基因型与三支血管病变风险增加相关(GC与GG相比:OR=2.14,95%CI=1.20-3.79;GC/CC与GG相比:OR=2.06,95%CI=1.20-3.54)。当将三支血管病变受试者与非三支血管病变受试者进行比较时,rs11536889变异基因型与三支血管病变风险增加相关(GC与GG相比:OR=1.76,95%CI=1.12-2.75;GC/CC与GG相比:OR=1.83,95%CI=1.19-2.82)。TLR4 rs11536889多态性也与Gensini评分相关(P=0.02)。CC变异型和GC/CC基因型受试者的Gensini评分高于野生GG基因型受试者(61.28±1.84和57.64±34.82 vs. 51.27±34.57)。我们的结果表明,TLR4 rs11536889多态性是CAD发生发展中的一个新的遗传因素,影响CAD的范围和严重程度。