Determinants of Plasma Renin Activity

Konoshita, Tadashi; Nakaya, Takahiro; Sakai, Ai; Yamada, Mika; Ichikawa, Mai; Sato, Satsuki; Imagawa, Michiko; Fujii, Miki; Yamamoto, K.; Makino, Yasukazu; Arakawa, Kazuhisa; Suzuki, Jinya; Ishizuka, Tamotsu

doi:10.1097/md.0000000000000354

Cited by 9 publications

(8 citation statements)

References 36 publications

(34 reference statements)

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“…High heritability estimates were reported for plasma renin activity in a recent investigation,[ 9 ] and we have also demonstrated in a recent report that a renin gene variant was associated with plasma renin activity as a genetic factor [ 17 ]. Each PRA value by genotype for C-5312T tended to be in fair accordance with the tissue expression levels; however, they did not reach the level of statistical significance in this study.…”

Section: Discussionsupporting

confidence: 77%

“…REN C-5312T is one of the rare validated genetic variants with reports that have shown their effects at the genetic transcriptional level[ 16 ] and also at the plasma activity level. [ 17 ] In this study, we evaluated the renal expression level of REN in human renal tissues in respect to REN genetic variants for the first time. Tissue expression levels of REN were significantly higher in T allele homozygotes than in heterozygotes and C allele homozygotes.…”

Section: Discussionmentioning

confidence: 99%

“…The levels of transcription were 45% greater with the 5312T variant than with the 5312C variant. [ 16 ] Recently, we have demonstrated that variations in the renin gene were associated with plasma renin activity as a genetic factor[ 17 ] and also that such variations are pharmacogenetic determinants of the antihypertensive effect of angiotensin receptor blockers. [ 18 , 19 ]…”

Section: Introductionmentioning

confidence: 99%

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A Genetic Variant in the Distal Enhancer Region of the Human Renin Gene Affects Renin Expression

et al. 2015

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BackgroundThe 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.MethodsSixty-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.ResultsLogarithmically 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.ConclusionThe 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.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Genetic Variant in the Distal Enhancer Region of the Human Renin Gene Affects Renin Expression

et al. 2015

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“…Recent studies of the human renin revealed the transcriptional mechanism [ 5 – 7 ], the gene expression [ 12 ] and genetic and environmental factors [ 13 ]. CCB is thought to up-regulate renin gene transcription via catecholamines–β1 adrenoceptor–cAMP–PKA–CREB–CRE pathway [ 14 ] and Ca–Ref1–nCaRE pathway [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

On the top of ARB N/L type Ca channel blocker leads to less elevation of aldosterone

et al. 2016

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The activation of the renin–angiotensin system (RAS) is one of the unfavourable characteristics of calcium channel blocker (CCB). N type calcium channel is thought to be involved in renin gene transcription and adrenal aldosterone release. Accordingly, N/L type CCB has a possibility of less elevation of plasma aldosterone concentrations (PAC) among CCBs. In a monotherapy study, we had already demonstrated that N/L type CCB leads to less activation of the RAS compared with L type CCB. The objective of this study is to substantiate the hypothesis that at the condition of additive administration on the top of an angiotensin receptor blocker (ARB), still N/L type CCB leads to less elevation of PAC compared with L type one. Subjects were 60 hypertensives administered with valsartan. As an open label study, amlodipine (L type) or cilnidipine (N/L type) were administered on the top of valsartan (ARB) in a cross-over manner. Results were as follows (valsartan+amlodipine compared with valsartan+cilnidipine): systolic blood pressure (SBP)/diastolic blood pressure (DBP) (mmHg): 132±10/76±10 compared with 131±10/77±9, P=0.95/0.48, plasma renin activity (PRA) (ng/ml·h): 2.41±2.67 compared with 2.00±1.50 P=0.20, PAC (pg/ml): 77.3±31.0 compared with 67.4±24.8, P<0.05, urinary albumin excretion (UAE) (mg/gCr): 105.9±216.1 compared with 73.9±122.2, P<0.05. Thus, PAC at cilnidipine was significantly lower than those at amlodipine in spite of the comparable BP reductions. Besides, UAE was significantly lower at cilnidipine. In conclusion, on the top of the ARB, it is suggested that cilnidipine administration might lead to less elevation of PAC and reduction in UAE compared with amlodipine.

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“…In the article “Determinants of Plasma Renin Activity Role of a Human Renin Gene Variant as a Genetic Factor”, 1 which appeared in Volume 93, Issue 29 of Medicine , an rs number at the end of the Subjects and Methods section was incorrectly presented. In the sentence “Recently, the variant C-5312T is assayed using the TaqMan method (rs 12750854) with common PCR conditions recommended by the manufacturer (Applied Biosystems, Foster City, CA),” rs 12750854 should have read rs 12750834.…”

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confidence: 99%