Zhao Chen, Wang Yun-ying, Xiao Zhi-xiu, Wang Yan-ping, Zhang Qi-yi
Department of Cardiology, Qingdao Municipal Hospital, Qingdao, Shandong, 266011 P. R. China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2007 Aug;24(4):428-31.
To analyze the association of transforming growth factor-beta1(TGF-beta1) gene +869T/C polymorphism and the serum level of TGF-beta1 in patients with early essential hypertension and early renal injury. To study the effect of the gene polymorphism of TGF-beta1 on the individual treatment with valsartan.
Eighty patients with early essential hypertension and early renal injury were treated with valsartan, and their polymorphism of TGF-beta1 gene +869T/C was analyzed by sequence specific primers-polymerase chain reaction method. Before valsartan treatment and 8 weeks after the treatment, their urinary microamount albumin (MA) levels were determined by using radioimmunity method, and their serum levels of TGF-beta1 were determined by enzyme-linked immunosorbent assay.
The blood pressure level of patients with TGF-beta 1 gene +869 CC genotype, TT genotype, TC genotype showed no significant difference (P> 0.05) before treatment. The urinary MA level of the three genotypes was CC genotype's > TC genetype's > TT genotype's in sequence, and the urinary MA level of CC genotype was significantly higher than that of TC genotype and of TT genotype (P< 0.01). The serum levels of TGF-beta1 in the three genotypes was CC genotype's > TC genotype's > TT genotype's in sequence (P< 0.01). There was statistically significant positive correlation between the urinary MA level and the serum level of TGF-beta1(P< 0.05). After 8 weeks treatment with valsartan, there was significant decrease of the blood pressure, the urinary MA level, and the serum level of TGF-beta1. However, the blood pressure reduction of the three types had no statistical significant difference in sequence. The absolute value of urinary MA reduction was CC genotype's > TC genotype's > TT genotype's in sequence, the reduction absolute value of urinary MA in CC genotype was higher than that of TC genotype and of TT genotype (P< 0.05), but the reduction percentage of the urinary MA in the three genotypes showed no statistically significant difference (P> 0.05). The reduction of serum levels of TGF-beta1 was CC genotype's > TC genotype's > TT genotype's in sequence, there was significant difference between each other (P< 0.01). However, the reduction percentage of the serum level of TGF-beta 1 in the three types showed no statistically significant difference (P> 0.05).
(1) The renal injury of CC genotype in patients with early essential hypertension and early renal injury is more serious than that of TC genotype and of TT genotype. (2)The serum level of TGF-beta 1 can accurately indicate the severity of the renal injury and the protective effect on kidney with valsartan in patients with essential hypertension and early renal injury. (3)The treatment effect of valsartan in the patients with different TGF-beta 1 +869T/C genotype has no difference, i.e., besides effectively decreasing the blood pressure and protecting the renal function, valsartan can reduce the serum level of TGF-beta1 without the influence of the gene polymorphism of TGF-beta1.
分析转化生长因子-β1(TGF-β1)基因+869T/C多态性与早期原发性高血压合并早期肾损伤患者血清TGF-β1水平的相关性。研究TGF-β1基因多态性对缬沙坦个体化治疗的影响。
80例早期原发性高血压合并早期肾损伤患者接受缬沙坦治疗,采用序列特异性引物-聚合酶链反应法分析其TGF-β1基因+869T/C多态性。在缬沙坦治疗前及治疗8周后,采用放射免疫法测定其尿微量白蛋白(MA)水平,采用酶联免疫吸附测定法测定其血清TGF-β1水平。
治疗前,TGF-β1基因+869CC基因型、TT基因型、TC基因型患者的血压水平无显著差异(P>0.05)。三种基因型的尿MA水平依次为CC基因型>TC基因型>TT基因型,CC基因型的尿MA水平显著高于TC基因型和TT基因型(P<0.01)。三种基因型的血清TGF-β1水平依次为CC基因型>TC基因型>TT基因型(P<0.01)。尿MA水平与血清TGF-β1水平呈显著正相关(P<0.05)。缬沙坦治疗8周后,血压、尿MA水平和血清TGF-β1水平均显著降低。然而,三种类型的血压降低无统计学显著差异。尿MA降低绝对值依次为CC基因型>TC基因型>TT基因型,CC基因型的尿MA降低绝对值高于TC基因型和TT基因型(P<0.05),但三种基因型的尿MA降低百分比无统计学显著差异(P>0.05)。血清TGF-β1水平降低依次为CC基因型>TC基因型>TT基因型,彼此间有显著差异(P<0.01)。然而,三种类型的血清TGF-β1水平降低百分比无统计学显著差异(P>0.05)。
(1)早期原发性高血压合并早期肾损伤患者中,CC基因型的肾损伤比TC基因型和TT基因型更严重。(2)血清TGF-β1水平可准确反映原发性高血压合并早期肾损伤患者的肾损伤严重程度及缬沙坦对肾脏的保护作用。(3)缬沙坦对不同TGF-β1+869T/C基因型患者的治疗效果无差异,即缬沙坦除有效降低血压、保护肾功能外,还可降低血清TGF-β1水平,不受TGF-β1基因多态性的影响。