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肾素基因C-5312T位点的遗传变异增加肾素水平及对血管紧张素受体阻滞剂的舒张压反应。

Genetic Variants of C-5312T REN Increased Renin Levels and Diastolic Blood Pressure Response to Angiotensin Receptor Blockers.

作者信息

Rohman Mohammad Saifur, Dewi Satiti Ika Arum, Widodo Nashi, Lukitasari Mifetika, Sujuti Hidayat

机构信息

Department of Cardiology and Vascular Medicine, Faculty of Medicine, Saiful Anwar General Hospital, Brawijaya University, Malang 65141, Indonesia.

Biomedical Sciences, Faculty of Medicine, University of Brawijaya, Malang 65141, Indonesia.

出版信息

Int J Hypertens. 2015;2015:930631. doi: 10.1155/2015/930631. Epub 2015 Oct 1.

Abstract

Renin catalyzes the cleavage of angiotensinogen into angiotensin I. Genetic variant C-5312T of renin enhancer has been reported to increase in vitro renin gene transcription. However, no obvious in vivo study was performed to see the renin level in C-5312T when treated with angiotensin receptor blockers (ARB). Therefore, this study aimed to investigate the serum renin level and blood pressure response in ARB treated hypertensive patients. Single nucleotide polymorphism (SNP) of C-5312T was identified in 55 hypertensive patients by using multiplex PCR and renin serum level was assayed by ELISA. The data showed that the increase of serum renin levels after 5 months of ARB treatment was significantly higher in patients with CT/TT genotype (10 pg/mL) than those with CC genotype (4.08 pg/mL) (P = 0.025). Hypertensive patients with CT/TT genotypes also showed less diastolic pressure reduction than CC genotypes in hypertensive patients with valsartan treatment (P = 0.04) or telmisartan treatment (P = 0.03). Finally, these findings suggested that SNP of C-5312T REN enhancer might contribute to higher increased renin serum levels and less diastolic blood pressure response to ARB treatment.

摘要

肾素催化血管紧张素原裂解为血管紧张素I。据报道,肾素增强子的基因变体C-5312T可增加体外肾素基因转录。然而,尚未进行明显的体内研究来观察使用血管紧张素受体阻滞剂(ARB)治疗时C-5312T的肾素水平。因此,本研究旨在调查接受ARB治疗的高血压患者的血清肾素水平和血压反应。通过多重PCR在55例高血压患者中鉴定出C-5312T的单核苷酸多态性(SNP),并通过ELISA测定肾素血清水平。数据显示,ARB治疗5个月后,CT/TT基因型患者(10 pg/mL)的血清肾素水平升高显著高于CC基因型患者(4.08 pg/mL)(P = 0.025)。在接受缬沙坦治疗(P = 0.04)或替米沙坦治疗(P = 0.03)的高血压患者中,CT/TT基因型的高血压患者的舒张压降低也低于CC基因型。最后,这些发现表明,C-5312T肾素增强子的SNP可能导致血清肾素水平升高幅度更大,以及对ARB治疗的舒张压反应更小。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ece3/4606213/287d4d8aec00/IJHY2015-930631.001.jpg

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