Department of Cardiovascular Disease, Changzhou Second People's Hospital, Affiliated Nanjing Medical University, Changzhou, 213003, Jiangsu, China.
Mol Biol Rep. 2012 Jan;39(1):359-67. doi: 10.1007/s11033-011-0746-x. Epub 2011 May 15.
Vascular endothelial growth factor and its receptor the kinase domain receptor play critical roles in the pathogenesis of coronary artery disease. Periostin is an up-regulator of kinase domain receptor expression. The purpose of this study was to determine whether polymorphisms in periostin are associated with the risk of coronary artery disease. Two single nucleotide polymorphisms (SNP C-33G, SNP A-953T) within the promoter region were chosen for further analyses. A case-control study was carried out with patients of Han Chinese ethnicity, which consisted of 492 coronary artery disease cases and 498 controls. Genotyping was performed by means of PCR and restriction fragment length polymorphism (PCR-RFLP) and the plasma level of periostin was measured by enzyme-linked immunosorbent assay (ELISA). In our study, the TT genotype of SNP-A953T was present in the general Chinese population (3.5%), but not in the Han Chinese from Beijing Project (HAPMAP CHB). Plasma periostin concentrations were elevated significantly in patients with coronary artery disease (7.96±8.33 nmol/l) compared with those in healthy volunteers (3.93±1.71 nmol/l) (P=0.005). There was a significant correlation between the 953T genotype and the plasma level of periostin (r2=-0.490, P=0.039). The prevalence of the TT genotype in patients was associated with a slightly lower risk of coronary artery disease (OR=0.443, 95% CI=0.200-0.982), but was not significant after correction (OR=0.427, 95% CI=0.146-1.250). The periostin-33G allele frequency was not significantly different in cases versus controls. Our data suggest that plasma periostin level may serve as a biomarker for the risk of coronary artery disease, but the periostin polymorphisms SNPC-33G and SNPA-953T were not significantly associated with the risk of coronary artery disease in this Chinese population. Although a major effect of the SNPs in the periostin genes on coronary artery disease susceptibility was excluded, the effect of the A-953T SNP on susceptibility and protein expression needs further investigation.
血管内皮生长因子及其受体激酶结构域受体在冠状动脉疾病的发病机制中起着关键作用。骨膜蛋白是激酶结构域受体表达的上调因子。本研究的目的是确定骨膜蛋白的多态性是否与冠状动脉疾病的风险相关。选择启动子区域内的两个单核苷酸多态性（SNP C-33G，SNP A-953T）进行进一步分析。进行了一项汉族患者的病例对照研究，包括 492 例冠状动脉疾病患者和 498 例对照。通过聚合酶链反应和限制性片段长度多态性（PCR-RFLP）进行基因分型，酶联免疫吸附试验（ELISA）测量骨膜蛋白的血浆水平。在我们的研究中，SNP-A953T 的 TT 基因型存在于普通中国人群中（3.5%），但不存在于北京项目汉族人群（HAPMAP CHB）中。与健康志愿者（3.93±1.71 nmol/L）相比，冠状动脉疾病患者的血浆骨膜蛋白浓度显著升高（7.96±8.33 nmol/L）（P=0.005）。953T 基因型与骨膜蛋白的血浆水平之间存在显著相关性（r2=-0.490，P=0.039）。患者 TT 基因型的患病率与冠状动脉疾病的风险略低相关（OR=0.443，95%CI=0.200-0.982），但在校正后无显著性差异（OR=0.427，95%CI=0.146-1.250）。病例与对照组之间的骨膜蛋白-33G 等位基因频率无显著差异。我们的数据表明，血浆骨膜蛋白水平可能作为冠状动脉疾病风险的生物标志物，但在中国人群中，骨膜蛋白多态性 SNPC-33G 和 SNPA-953T 与冠状动脉疾病的风险无显著相关性。虽然排除了骨膜蛋白基因中的 SNPs 对冠状动脉疾病易感性的主要影响，但 A-953T SNP 对易感性和蛋白表达的影响需要进一步研究。
