A Genetic Variant in the Distal Enhancer Region of the Human Renin Gene Affects Renin Expression.
A Genetic Variant in the Distal Enhancer Region of the Human Renin Gene Affects Renin Expression.
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DOI：
10.1371/journal.pone.0137469
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Genomic Disease Outcome Consortium (G-DOC) Study Investigators
中科院分区：
文献类型：
--
作者：
Makino Y;Konoshita T;Omori A;Maegawa N;Nakaya T;Ichikawa M;Yamamoto K;Wakahara S;Ishizuka T;Onoe T;Nakamura H;Genomic Disease Outcome Consortium (G-DOC) Study Investigators
最近的研究证实了血浆肾素活性的高遗传度。位于人类肾素基因(REN)强增强子附近的一个变异C-5312T已被证明具有不同的转录活性水平，这取决于其等位基因：5312T等位基因的转录水平比5312C等位基因的转录水平高45%。本研究的目的是证实REN基因增强子区域的变异参与调节肾脏肾素表达的假说。经肾活检证实的肾病患者64例，男35例，女35例，年龄41.9±20.9岁，SBP/DBP为123.1±23.7/73.4±14.8 mm Hg，S-Cr0.93±0.63 mg/dl。采用聚合酶链式反应-限制性片段长度多态性和TaqMan方法对REN基因C-5312T进行了检测。一小部分肾皮质的总RNA被逆转录，并利用实时荧光定量聚合酶链式反应系统扩增出REN和GAPDH。经对数变换后的相对比值(10−3)为：CC(26例)，0.016±0.005；CT(33例)，0.047±0.021(p=0.41vs.CC)；TT(5例)，0.198±0.194(p=0.011 vs.CC，p<；0.031 vs.CT)。因此，REN的表达在不同的遗传变异体之间观察到显著的差异。结果表明，人肾素基因增强子区域的变异对肾素在肾组织中的表达水平有影响；这一观察结果与转录检测结果一致。
The high heritability of plasma renin activity was confirmed in recent investigations. A variation located near the strong enhancer of the human renin gene (REN), C-5312T, has been shown to have different transcription activity levels depending on its allele: the 5312T allele shows transcription levels that are 45% greater than those of the 5312C allele. The purpose of this study was to confirm the hypothesis that variations in the enhancer region of the REN gene are involved in regulating renal expression of renin. Sixty-four subjects with biopsy-proven renal diseases were included in this study (male/female: 35/29, age 41.9 ± 20.9 years, SBP/DBP 123.1 ± 23.7/73.4 ± 14.8 mmHg, s-Cr 0.93 ± 0.63 mg/dl). A genetic variant of REN, C-5312T, was assayed by PCR-RFLP and the TaqMan method. Total RNAs from a small part of the renal cortex were reverse-transcribed and amplified for REN and GAPDH with a real-time PCR system. Logarithmically transformed expression values of the relative ratio of REN to GAPDH (10−3) were as follows (mean ± SE): CC (26 cases), 0.016 ± 0.005; CT (33 cases), 0.047 ± 0.021 (p = 0.41 vs. CC); TT (5 cases), 0.198 ± 0.194 (p = 0.011 vs. CC, p < 0.031 vs. CT). Thus, significant differences in REN expression were observed among the genetic variants. The results suggest that variants in the enhancer region of the human renin gene have an effect on the expression levels of renin in renal tissue; this observation is in good accordance with the results of the transcriptional assay.