Liu Xueyan, Jiang Chao, Yang Ping
Department of Cardiology, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
Department of Hepatobiliary Pancreatic Surgery, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Mol Med Rep. 2017 Aug;16(2):1289-1297. doi: 10.3892/mmr.2017.6736. Epub 2017 Jun 9.
A previous study of the authors using microarray analysis indicated that the expression of complement component 4 binding protein (C4BP)A is upregulated in essential hypertension (EH) patients, but the association between C4BPA variations and EH has not yet been clearly demonstrated. Since the 5' upstream region is known to serve important roles in the gene expression regulation, the present study aimed to identify and analyze the association of single nucleotide polymorphisms (SNPs) in the 5' upstream region between the C4BPA gene with EH in a case‑control study among a northeastern Han Chinese population through direct sequencing as well as genotype detection. A total of 822 unrelated participants were included. The higher expression level of C4BPA in the peripheral blood of patients with EH was verified through reverse transcription‑quantitative polymerase chain reaction and ELISA. A total of four SNPs, rs73079108, rs74148971, rs77660718 and rs11120211 were identified in the 5' upstream region of C4BPA. Association analysis demonstrated that the genotypic frequencies of rs73079108 were significantly different between EH and the control groups (P=0.011), and A allelic frequency was lower in EH (P<0.001). Logistic regression analysis indicated that the rs73079108 polymorphism was closely associated with EH (AA:GA:GG genetic model: P=0.007, odds ratio (OR)=0.604, 95% confidence interval (CI) [0.418‑0.873]; AA+GA:GG genetic model: P=0.005, OR=0.806, 95% CI[0.382‑0.841]), and the A allele may be a protective factor. Subgroup analysis by sex and BMI presented concordant conclusions in female and non‑obese samples. Further analysis indicated that rs73079108 was associated with systolic blood pressure (P<0.001), diastolic blood pressure (P=0.001) and fast blood glucose (FBG) (P=0.021). In addition, rs73079108 GA and GG carriers reported a significant increase in the level of the protein encoded by C4BPA than those of AA carriers. The rs73079108 polymorphism in the 5' upstream region of C4BPA was associated with EH, and rs73079108‑A may be an independent predictor.
作者先前一项使用微阵列分析的研究表明，补体成分4结合蛋白（C4BP）A在原发性高血压（EH）患者中表达上调，但C4BPA变异与EH之间的关联尚未得到明确证实。由于已知5'上游区域在基因表达调控中起重要作用，本研究旨在通过直接测序以及基因型检测，在一项针对中国东北汉族人群的病例对照研究中，鉴定并分析C4BPA基因5'上游区域单核苷酸多态性（SNP）与EH的关联。共纳入822名无亲属关系的参与者。通过逆转录定量聚合酶链反应和酶联免疫吸附测定法验证了EH患者外周血中C4BPA的较高表达水平。在C4BPA的5'上游区域共鉴定出4个SNP，即rs73079108、rs74148971、rs77660718和rs11120211。关联分析表明，rs73079108的基因型频率在EH组和对照组之间存在显著差异（P = 0.011），且EH组中A等位基因频率较低（P < 0.001）。逻辑回归分析表明，rs73079108多态性与EH密切相关（AA:GA:GG遗传模型：P = 0.007，比值比（OR）= 0.604，95%置信区间（CI）[0.418 - 0.873]；AA + GA:GG遗传模型：P = 0.005，OR = 0.806，95% CI[0.382 - 0.841]），且A等位基因可能是一个保护因素。按性别和BMI进行的亚组分析在女性和非肥胖样本中得出了一致的结论。进一步分析表明，rs73079108与收缩压（P < 0.001）、舒张压（P = 0.001）和空腹血糖（FBG）（P = 0.021）相关。此外，rs73079108的GA和GG携带者报告的C4BPA编码蛋白水平比AA携带者显著升高。C4BPA基因5'上游区域的rs73079108多态性与EH相关，且rs73079108 - A可能是一个独立预测因子。
