CYP3A5 polymorphism and sensitivity of blood pressure to dietary salt in Japanese men

Miyaki, Koichi; Wang, Wei; Muramatsu, Masaaki

doi:10.1038/jhh.2009.74

Cited by 27 publications

(21 citation statements)

References 24 publications

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“…This indicated that the CYP3A5 rs776746 polymorphism might be a risk factor for salt sensitivity. 40 The underlying biological mechanism by which CYP3A5 exerts its effects on the pathogenesis of hypertension is still not known. As a potential intermediate phenotype, cortisol may have an important role in the regulation of BP levels and the development of hypertension.…”

Section: Discussionmentioning

confidence: 99%

“…27,29,31,32,[35][36][37][38][39][40] As shown in Figures 2 and 3, there was evidence of heterogeneity between studies (systolic BP (SBP): Figure 4 and Table 3). The stability of these results was also confirmed by sensitivity analysis (data not shown).…”

Section: Characteristics Of the Studiesmentioning

confidence: 96%

“…30 Therefore, 12 papers met the inclusion criteria and were included in the meta-analysis. 27,29,[31][32][33][34][35][36][37][38][39][40] Individuals carrying at least one CYP3A5*1 allele were combined as CYP3A5*1 carriers in one group (high expression), and individuals without a CYP3A5*1 allele were combined as CYP3A5*1 non-carriers in the other group (low expression). The characteristics of the included studies are listed in Tables 1 and 2.…”

Section: Characteristics Of the Studiesmentioning

confidence: 99%

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Association of the CYP3A5 polymorphism (6986G>A) with blood pressure and hypertension

Wang

Liu

et al. 2011

Hypertens Res

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The cytochrome P450 family 3 subfamily A polypeptide 5 (CYP3A5) gene has been implicated in the regulation of blood pressure (BP) and thus, may serve as a potential risk factor for the development of hypertension. However, current results regarding the association between CYP3A5 single nucleotide polymorphisms and BP/hypertension have been inconsistent. In this study, we performed a meta-analysis to evaluate the association between the CYP3A5 rs776746 (6986G4A) polymorphism and BP/hypertension. Ten studies (representing 2799 cases and 6794 controls) were included to determine the association of this single nucleotide polymorphism with hypertension, and 12 studies (9076 subjects) were included to determine the association of this single nucleotide polymorphism with BP. Overall, no associations were observed between the rs776746 polymorphism and BP/hypertension. In subgroup analysis, CYP3A5*1 carriers had lower systolic BP, compared with non-carriers in white populations (mean difference¼À1.322, 95% confidence interval À2.401 to À0.242 mm Hg, P¼0.016). This meta-analysis suggested a modestly significant association between the CYP3A5 rs776746 polymorphism and systolic BP in white populations. Given the limited sample size, additional studies are necessary to investigate the role of CYP3A5 in the regulation of BP and the pathogenesis of hypertension. Hypertension Research (2011Research ( ) 34, 1216Research ( -1220 doi:10.1038/hr.2011; published online 4 August 2011Keywords: blood pressure; cytochrome P450 3A5; meta-analysis INTRODUCTIONHypertension affects nearly one-third of the adult population worldwide and is associated with stroke and cardiovascular disease, which are major contributors to the global health burden. 1 Although lifestyle factors (for example, excess sodium intake and lack of physical activity) can contribute to elevated blood pressure (BP) and increased hypertension risks, 2 genetic factors have also been implicated in the pathogenesis of these diseases. [3][4][5] Genome-wide association studies have identified many genetic variants that may be associated with hypertension. 6 These exciting new results elucidating hypertension's underlying molecular mechanisms have greatly expanded our knowledge and provided new insights into the etiology of hypertension. 7 The cytochrome P450 family 3 subfamily A polypeptide 5 (CYP3A5) gene encodes a member of the cytochrome P450 super family of enzymes. The CYP3A5 gene is part of a cluster of cytochrome P450 genes on chromosome 7q21.1. 8 Cytochrome P450 proteins are monooxygenases that have an important role in the metabolism of both endogenous substances (for example, hormones) and exogenous substances (for example, drugs). 9,10 Cytochrome P450 proteins are expressed in an organ-specific manner, with CYP3A5 predominantly expressed in the kidney. 11 As a glucocorticoid 6b-hydroxylase, the CYP3A5 enzyme converts cortisol or corticosterone to 6b-corticosterone, which may lead to increased sodium and water retention. 12,13 The CYP3A5 gene has a common polymorphis...

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Section: Discussionmentioning

confidence: 99%

Section: Characteristics Of the Studiesmentioning

confidence: 96%

Section: Characteristics Of the Studiesmentioning

confidence: 99%

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Association of the CYP3A5 polymorphism (6986G>A) with blood pressure and hypertension

Wang

Liu

et al. 2011

Hypertens Res

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“…Data suggested a role for CYP3A5 in salt-sensitive blood pressure regulation and indicated an association with hypertension (Givens et al, 2003;Kreutz et al, 2004Kreutz et al, , 2005Ho et al, 2005;Kivistö et al, 2005;Bochud et al, 2006;Lieb et al, 2006;Eap et al, 2007;Langaee et al, 2007;Zhang et al, 2010). Although controversial results regarding this association have been obtained, it has been hypothesized that CYP3A5 modifies renal tubular sodium reabsorption via protection of the mineralocorticoid receptor from glucocorticoid binding in the distal tubular cells Kreutz et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

CYP3A5 Genotype-Phenotype Analysis in the Human Kidney Reveals a Strong Site-Specific Expression of CYP3A5 in the Proximal Tubule in Carriers of the *CYP3A5**1 Allele

Bolbrinker¹,

Seeberg²,

Schostak³

et al. 2012

Drug Metab Dispos

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ABSTRACT:Interindividual variability in the drug-metabolizing activity of the CYP3A5 enzyme is mainly due to a single nucleotide polymorphism in CYP3A5, leading to low expression in homozygous CYP3A5*3/*3 individuals compared with CYP3A5*1 allele carriers. In the human kidney, expression of CYP3A5 has been implicated in blood pressure regulation and calcineurin inhibitor-associated nephrotoxicity. The effect of the CYP3A5*1/*3 polymorphism on the expression level and protein distribution within the human kidney is not well characterized. Therefore, we performed a genotype-phenotype analysis of CYP3A5 mRNA and protein expression in the human kidney. To this end, we analyzed sections of normal kidney tissue obtained from 93 white individuals undergoing nephrectomy by quantitative mRNA expression analysis. Qualitative protein expression analysis of CYP3A5 was performed by immunohistochemistry. Mean renal mRNA expression of carriers of the CYP3A5*1 (n ‫؍‬ 12) allele was more than 18-fold higher than that of CYP3A5*3/*3 carriers (n ‫؍‬ 81, p < 0.001). Immunohistochemical analysis demonstrated CYP3A5 protein in all epithelia of the nephron in kidney sections with the CYP3A5*3/*3 genotype. In carriers of the CYP3A5*1 allele, a strong increase in protein expression of CYP3A5 was detected, and this was confined to the proximal tubule. This study confirms a significant effect of the CYP3A5*1/*3 polymorphism on CYP3A5 expression in the normal human kidney and reveals a strong nephron segment-specific difference in the CYP3A5 protein expression limited to the proximal tubule.

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“…Although not identified in GWAS, another CYP450 candidate on the list is CYP3A5 [13][14][15][16][17], but the most studied CYP450 gene in blood pressure control remains the aldosterone synthase CYP11B2 [18]. Considering the dual role of CYP450 enzymes in the metabolism of exogenous (e.g.…”

Section: See Original Paper On Page 56mentioning

confidence: 97%

CYP2C9 variants and blood pressure response to salt: when salt sensitivity meets pharmacogenomics

Bochud¹

2011

Journal of Hypertension

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CYP3A5 polymorphism and sensitivity of blood pressure to dietary salt in Japanese men

Cited by 27 publications

References 24 publications

Association of the CYP3A5 polymorphism (6986G>A) with blood pressure and hypertension

Association of the CYP3A5 polymorphism (6986G>A) with blood pressure and hypertension

CYP3A5 Genotype-Phenotype Analysis in the Human Kidney Reveals a Strong Site-Specific Expression of CYP3A5 in the Proximal Tubule in Carriers of the *CYP3A5**1 Allele

CYP2C9 variants and blood pressure response to salt: when salt sensitivity meets pharmacogenomics

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CYP3A5 polymorphism and sensitivity of blood pressure to dietary salt in Japanese men

Cited by 27 publications

References 24 publications

Association of the CYP3A5 polymorphism (6986G>A) with blood pressure and hypertension

Association of the CYP3A5 polymorphism (6986G>A) with blood pressure and hypertension

CYP3A5 Genotype-Phenotype Analysis in the Human Kidney Reveals a Strong Site-Specific Expression of CYP3A5 in the Proximal Tubule in Carriers of the CYP3A5*1 Allele

CYP2C9 variants and blood pressure response to salt: when salt sensitivity meets pharmacogenomics

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CYP3A5 Genotype-Phenotype Analysis in the Human Kidney Reveals a Strong Site-Specific Expression of CYP3A5 in the Proximal Tubule in Carriers of the *CYP3A5**1 Allele