ACE2基因多态性对厄贝沙坦治疗2级高血压伴慢性肾衰患者疗效的影响

doi:10.12092/j.issn.1009-2501.2018.06.010

中国临床药理学与治疗学 ›› 2018, Vol. 23 ›› Issue (6): 661-666.doi: 10.12092/j.issn.1009-2501.2018.06.010

ACE2基因多态性对厄贝沙坦治疗2级高血压伴慢性肾衰患者疗效的影响

孟晶茜¹，赵瑛瑛¹，张文吉¹，张宛哲¹，申鹏霄¹，刘丁¹，苏晨皓¹，沈杰²，王建生¹

¹郑州大学第二附属医院肾病风湿科，郑州 450000，河南；²皖南医学院弋矶山医院临床药学部，芜湖 241001，安徽

收稿日期:2017-12-14 修回日期:2018-03-23 出版日期:2018-06-26 发布日期:2018-06-19
通讯作者: 王建生，女，硕士研究生，主任医师，研究方向：肾小球疾病。 Tel:13603849857 E-mail：wjs9857@sina.com
作者简介:孟晶茜，女，硕士研究生，主治医师，研究方向：肾小球疾病。 Tel:13783595634 E-mail：mengjingqian@126.com
基金资助:
国家自然科学基金（81641141）

Effects of ACE2 polymorphism on the clinical outcomes of irbesartan for the treatment of stage 2 hypertension concomitant with chronic renal failure

MENG Jingqian¹, ZHAO Yingying¹, ZHANG Wenji ¹, ZHANG Wanzhe ¹, SHEN Pengxiao ¹，LIU Ding ¹, SU Chenhao¹, SHEN Jie ², WANG Jiansheng¹

¹ Department of Nephrology and Rheumatism,the Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450000，Henan, China; ²Department of Clinical Pharmacy, Yijishan Hospital of Wannan Medical College, Wuhu 241001, Anhui, China

Received:2017-12-14 Revised:2018-03-23 Online:2018-06-26 Published:2018-06-19

摘要/Abstract

摘要：

目的：探讨ACE2基因多态性对厄贝沙坦治疗2级高血压伴慢性肾衰患者的疗效的影响。方法：在肾内科入组2级高血压伴肾衰患者135例，给予单药厄贝沙坦片，每天150～300 mg，4周后评价降压效果，测定血清肌酐（Scr）和血尿素氮（BUN）水平并进行比较。用限制性片段长度多态性聚合酶链反应（PCR-RFLP）对ACE2 G8790A位点进行基因分型。并比较不同基因型患者的降压情况、血清肌酐以及尿素氮水平。结果：与治疗前的基础血压相比，经过厄贝沙坦治疗之后患者的收缩压（SBP）和舒张压（DBP）均有较大幅度的下降，差异具有统计学意义（P<0.01）。同时，与治疗前的肾功能状态相比，经过厄贝沙坦治疗之后患者的Scr和BUN均具有明显下降，且差异具有统计学意义（P<0.05）。在基因型方面，ACE2 G8790A位点则有较多的变异，基因分型结果显示野生型TT型64例，TC型58例，CC型13例，最小等位基因频率为0.31，三种基因型分布符合哈迪温伯格平衡（P=0.979）。基于基因型的结果表明，C等位基因携带者可以显著影响厄贝沙坦的降压效果， TC型和CC型患者相对于野生型TT型患者来说，无论是收缩压（SBP）还是舒张压（DBP），降压效果均较差，结果差异均具有统计学意义（P=0.018和P=0.021）。血清肌酐以及血尿素氮水平，三组基因型患者并没有明显的差异。结论:厄贝沙坦可以显著改善2级高血压伴慢性肾衰患者的疾病症状，ACE2的G8790A位点可能影响厄贝沙坦的降压效果，但对厄贝沙坦改善肾功能方面没有太大的影响。

关键词: 厄贝沙坦, 高血压, 慢性肾衰, ACE2, 多态性

Abstract:

AIM: To investigate the effects of ACE2 gene polymorphism on the treatment of irbesartan for the patients with stage-2 hypertension concomitant with chronic renal failure. METHODS: A total of 135 patients with stage-2 hypertension concomitant with chronic renal failure in the department of nephrology and rheumatism were included in this study. All of the patients were given irbesartan 150-300 mg once daily. After 4 weeks treatment, the antihypertensive effect were evaluated, the serum creatinine (Scr) and blood urea nitrogen (BUN) were determined. Genotyping of polymorphism of ACE2 G8790A were performed using the restriction fragment length polymorphic polymerase chain reaction (PCR-RFLP). The blood pressure and Scr and BUN levels in different genotypes were compared. RESULTS:Compared with the pre-treatment baseline blood pressure, The SBP and DBP in patients after irbesartan treatment were significantly reduced, and there was a significant statistical difference (P<0.01). At the same time, compared with the state of renal function before treatment, the Scr and BUN were both significantly reduced in patients after irbesartan treatment, and there was a statistically significant difference (P< 0.05). In terms of genotypes, ACE2 gene G8790A sites, on the other hand, there were more variations, the genotyping results show that the wild type TT 64 cases, 58 cases of TC genotype, CC genotype 13cases, the minimum allele frequency was 0.31, the genotypes distribution in accordance with hardy-weinberg equilibrium (P=0.979). Based on genotypes, the results showed that the decrease of blood pressure in patients with TT genotypes were significantly higher than that of TC and CC genotypes patients, and the results were statistically significant (P=0.018). However, there was no significant difference in the serum creatinine and blood urea nitrogen according to the three groups of genotypes. CONCLUSION: Irbesartan may help the patients with stage-2 hypertension concomitant with chronic renal failure by relieving the disease symptoms. ACE2 G8790A polymorphism may influence the antihypertensive effect of irbesartan treatment. However, there was no significant effect of the polymorphism on the clinical outcomes for irbesartan improvement in renal function.

Key words: irbesartan, hypertension, chronic renal failure, ACE2, polymorphism

中图分类号:

R968

孟晶茜，赵瑛瑛，张文吉，张宛哲，申鹏霄，刘丁，苏晨皓，沈杰，王建生. ACE2基因多态性对厄贝沙坦治疗2级高血压伴慢性肾衰患者疗效的影响[J]. 中国临床药理学与治疗学, 2018, 23(6): 661-666.

MENG Jingqian, ZHAO Yingying, ZHANG Wenji, ZHANG Wanzhe, SHEN Pengxiao，LIU Ding, SU Chenhao, SHEN Jie, WANG Jiansheng. Effects of ACE2 polymorphism on the clinical outcomes of irbesartan for the treatment of stage 2 hypertension concomitant with chronic renal failure[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(6): 661-666.

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ACE2基因多态性对厄贝沙坦治疗2级高血压伴慢性肾衰患者疗效的影响

Effects of ACE2 polymorphism on the clinical outcomes of irbesartan for the treatment of stage 2 hypertension concomitant with chronic renal failure

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