Angiotensin-converting enzyme (ACE) I/D genotype and renal ACE gene expression

Mizuiri, Sonoo; Hemmi, Hiromichi; Kumanomidou, Haruko; Iwamoto, Masateru; Miyagi, Moriatsu; Sakai, Ken; Aikawa, Atsushi; Ohara, Takahiro; Yamada, Kazuo; Shimatake, Hiroyuki; Hasegawa, Akira

doi:10.1046/j.1523-1755.2001.0600031124.x

Cited by 76 publications

(68 citation statements)

References 25 publications

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“…These differences were confirmed by immunohistochemistry, with more ACE staining in tubules and kidney vessels of WU-B. This corresponds with the human plasma and tissue variation in relation to the ACE I/D genotype (Mizuiri et al 2001;Rigat et al 1990). To identify the physiologic mechanisms of the genetic modulation of ACE activity, we measured the ACE mRNA expression.…”

Section: Discussionsupporting

confidence: 70%

“…Genetically, deletion in intron 16 of the human ACE gene results in an increased ACE activity in both plasma and tissue level (Danser et al 1995;Mizuiri et al 2001;Rigat (Ng et al 2005;Staessen et al 1997). Whereas meta-analyses confirm a role for the D allele as a renal and cardiovascular risk factor (Samani et al 1996), the significance of genetically high/low ACE is still controversial (Staessen et al 1997).…”

Section: Discussionmentioning

confidence: 99%

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Differential ACE expression among tissues in allele-specific Wistar rat lines

et al. 2009

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In humans, the insertion/deletion polymorphism in the angiotensin converting enzyme (ACE) gene accounts for half of the variance in plasma ACE activity. The deletion allele is associated with high plasma ACE activity, cardiovascular disease, and renal disease. In rat, a similar association is found between the B and L alleles of a microsatellite marker in the ACE gene. We identified the B/L variation in the Wistar outbred rat and bred two lines homozygous for the two alleles (WU-B and WU-L). ACE activity was measured in serum, heart, kidney, and aorta homogenates. Immunohistochemistry and ACE mRNA expression were performed in heart, kidney, and aortic tissue. Aortic rings were collected and stimulated with AngI, AngII, and AngI with Lisinopril to measure ACE functional activity by vasoconstrictor response. Serum, heart, and kidney ACE activity and kidney mRNA expression were two-fold higher in WU-B. Kidney staining showed a clear difference in tubular ACE expression, with more staining in WU-B. While in aorta ACE activity and mRNA expression was twofold higher in WU-L, functional conversion of AngI was higher in WU-B, indicating either a functional difference in AngI to AngII conversion between the two alleles due to different splicing or the presence of other factors involved in the conversion that are differentially expressed as the result of differences in the ACE alleles. The newly developed WU-B and WU-L lines show tissue-specific differences in ACE expression and activity. This provides an experimental tool to study the pathophysiologic consequences of differences in ACE alleles in renal and cardiovascular disease.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Differential ACE expression among tissues in allele-specific Wistar rat lines

et al. 2009

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“…Several studies correlated gene expression levels in native biopsies with histologic parameters (27,36,37). Further correlations found included the Th1/Th2 chemokine expression profiles with the clinical outcomes in glomerulonephritis (47,48), the angiotensin-converting enzyme (ACE) expression with the ACE-genotype of the patients (49), and the renin mRNA levels with the medical therapy by ACE inhibition (50). In renal transplants, mRNA expression of inflammatory mediators has been shown to correlate with acute rejection (51)(52)(53).…”

Section: Sensitive Assays For Renal Gene Expression Have Been Developedmentioning

confidence: 99%

Repuncturing the Renal Biopsy

Kretzler¹,

Cohen²,

Doran³

et al. 2002

Journal of the American Society of Nephrology

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“…An insertion/deletion (I/D) polymorphism in the 16th intron of the ACE gene was reported to be associated with blood pressure and plasma levels of ACE (Rigat et al 1990). The I/D polymorphism has also been reported to be associated with renal expression of ACE (Mizuiri et al 2001) as well as susceptibility to diabetic nephropathy. The association of CSNP with substitution of methionine at codon 235 to threonine (M235T) in AGT and a SNP in the 3¢UTR of AGTR1 (A1166C) with diabetic nephropathy has also been examined.…”

Section: Introductionmentioning

confidence: 99%

Combinational effect of genes for the renin–angiotensin system in conferring susceptibility to diabetic nephropathy

et al. 2006

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To elucidate the role of the renin-angiotensin system (RAS) in diabetic nephropathy, we examined the association between diabetic nephropathy in a large cohort of Japanese type 2 diabetic patients and polymorphisms within the genes that encode angiotensin-converting enzyme (ACE), angiotensinogen (AGT) and angiotensin II receptor type 1 (AGTR1). Single nucleotide polymorphisms (SNPs) within these genes were genotyped using invader assay in 747 nephropathy cases and 557 control subjects. Eight SNPs within the ACE gene were significantly associated with diabetic nephropathy (P<0.05), including five SNPs in almost complete linkage disequilibrium to the insertion/deletion polymorphism in the 16th intron (P=0.01, odds ratio =1.34, 95% CI 1.07-1.69). Three SNPs within the AGT, including M235T and one SNP in the AGTR1, were also significantly associated with nephropathy (M235T P=0.01, odds ratio =0.74, 95% CI 0.59-0.94). In addition, we found that the allelic mRNA expression corresponding to the 235M allele was significantly higher than that for the 235T allele in normal kidney tissues. Furthermore, we found a significant additional effect of these three genes by a step-wise logistic regression analysis (final empirical P value =0.00005). We concluded that RAS gene polymorphisms may contribute to the susceptibility to diabetic nephropathy in type 2 diabetes.

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Angiotensin-converting enzyme (ACE) I/D genotype and renal ACE gene expression

Abstract: It is suggested that renal ACE gene expression is associated with the ACE I/D genotype in healthy Japanese subjects.

Cited by 76 publications

References 25 publications

Differential ACE expression among tissues in allele-specific Wistar rat lines

Differential ACE expression among tissues in allele-specific Wistar rat lines

Repuncturing the Renal Biopsy

Combinational effect of genes for the renin–angiotensin system in conferring susceptibility to diabetic nephropathy

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