细胞色素 11B2 醛固酮合酶基因 rs1799998 单核苷酸多态性决定了醛固酮升高、血压升高和肾小球滤过率降低，尤其是在糖尿病女性患者中。

The cytochrome 11B2 aldosterone synthase gene rs1799998 single nucleotide polymorphism determines elevated aldosterone, higher blood pressure, and reduced glomerular filtration, especially in diabetic female patients.

机构信息

Bukovinian State Medical University, Chernivtsi, Ukraine.

St. Anna Hospital, Herne, Germany.

出版信息

Endocr Regul. 2020 Jul 1;54(3):217-226. doi: 10.2478/enr-2020-0024.

DOI:10.2478/enr-2020-0024

PMID:32857720

Abstract

OBJECTIVE

The cytochrome 11B2 aldosterone synthase gene (CYP11B2) that links to aldosterone synthase enzyme synthesis changes and blood pressure regulation is of particular interest among the renin-angiotensin-aldosterone system encoding genes.

METHODS

One-hundred hypertensive patients with target-organ damaging (2nd stage), moderate, high or very high cardiovascular risk were involved in the case-control study. Mean age was 59.87±8.02 years. Diabetes Mellitus type 2 (DM2) was in 28 persons. Chronic kidney disease (CKD) was diagnosed in 29 persons according to the National Kidney Foundation recommendations (2012) after glomerular filtration rate (GFR) decline <60 ml/min/1.73m2 for ≥3 months (measured by CKD-EPI equations). Aldosterone, cystatin-C, and creatinine levels were measured in serum. Control group included 48 practically healthy persons of relevant age. Gene's nucleotide polymorphism CYP11B2 (-344C/T) was examined by polymerase chain reaction.

RESULTS

CKD evolution in hypertensive patients followed by higher systolic and diastolic blood pressure (SBP, DBP) values increased creatinine, cystatin-C, and aldosterone serum concentrations by 28.76%, 28.41% and 29.43% (р<0.05), respectively. Polymorphic site of CYP11B2 (rs1799998) gene is associated with SBP and DBP increase (p<0.05), reduced GFR preferably calculated by CKDEPI-cystatin C (F=10.79-14.45; p<0.001) and elevated aldosterone content (F=55.84; p<0.001), creatinine and cystatin-С as well (F=4.16-5.08; p<0.05) mainly in the ТТ-genotype female carriers (p<0.001). Hypertensive women with DM2 demonstrated stronger relations of CYP11B2 gene polymorphic site with the increased aldosterone content (F=47.52; p<0.001), than women without DM2 (p<0.001) and male patients (p=0.014).

CONCLUSIONS

Genetic variations involving CYP11B2 might influence the kidney function, hypertension course, and severity via aldosterone secretion upregulation.

摘要

目的

与醛固酮合酶酶合成变化和血压调节相关的细胞色素 11B2 醛固酮合酶基因（CYP11B2）是肾素-血管紧张素-醛固酮系统编码基因中特别引人关注的一个。

方法

本病例对照研究纳入了 100 名患有靶器官损害（2 期）、中度、高度或极高心血管风险的高血压患者。平均年龄为 59.87±8.02 岁。28 人患有 2 型糖尿病（DM2）。根据肾小球滤过率（GFR）下降<60 ml/min/1.73m2 持续≥3 个月（采用 CKD-EPI 方程测量），29 人被诊断为慢性肾脏病（CKD）。血清中测量了醛固酮、胱抑素-C 和肌酐水平。对照组包括 48 名年龄相匹配的健康人。通过聚合酶链反应检测 CYP11B2（-344C/T）基因的核苷酸多态性。

结果

高血压患者的 CKD 进展导致收缩压和舒张压（SBP、DBP）值升高，血清中肌酐、胱抑素-C 和醛固酮浓度分别升高 28.76%、28.41%和 29.43%（p<0.05）。CYP11B2 基因（rs1799998）多态性位点与 SBP 和 DBP 升高（p<0.05）相关，CKDEPI-胱抑素 C 计算的肾小球滤过率（F=10.79-14.45；p<0.001）和醛固酮含量升高（F=55.84；p<0.001），以及肌酐和胱抑素-C（F=4.16-5.08；p<0.05），主要在 TT 基因型女性携带者中（p<0.001）。患有 2 型糖尿病的高血压女性与 CYP11B2 基因多态性位点与升高的醛固酮含量之间的关系更强（F=47.52；p<0.001），而不患有 2 型糖尿病的女性（p<0.001）和男性患者（p=0.014）。