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

Abstract

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...

Pregnane X Receptor Activator Rifampin Increases Blood Pressure and Stimulates Plasma Renin Activity

“…A meta-analysis suggested that, although there was no overall effect of CYP3A5 expressor status on BP or hypertension, in white populations, the carriers of functional CYP3A5*1 allele had lower systolic BP compared with noncarriers. 47 In addition to CYP3A4, the polymorphic CYP3A5 enzyme is involved in the synthesis of 4βHC 9 and the concentration of 4βHC increases stepwise with the number of CYP3A5*1 alleles present. 9 Thus, as CYP3A5*1 carriers have higher circulating 4βHC concentration than CYP3A5 nonexpressors, 9 this would be consistent with our finding that higher 4βHC is associated with lower 24-hour BP.…”

PharmGKB summary

“…Studies showing an association of the * 1 allele with higher blood pressure or with hypertension have all been carried out in individuals of African descent or in older White individuals [49]. In a recent meta-analysis (for hypertension: 10 studies including more than 9500 individuals, and for blood pressure: 12 studies including more than 9000 individuals), no association was found overall with the CYP3A5 genotype, and, in Whites, a modest association was observed between * 1 and lower systolic blood pressure [50]. …”

Non-HLA Genetic Factors and Their Influence on Heart Transplant Outcomes: A Systematic Review

“…The cytochrome P450 family 3, subfamily A, member 5 ( CYP3A5 ) gene on chromosome 7 encodes an enzyme of the cytochrome P450 family, mostly expressed in the liver, which is involved in the metabolism of a large variety of drugs and the synthesis of cholesterol and other lipids. 38 CYP3A5 is known to be involved in the development of essential hypertension in humans 39 and to influence the required dose of the calcineurin inhibitors cyclosporin and tacrolimus in solid organ transplantation recipients. The rs776746 G allele is a loss-of-function allele, which disrupts a splice site.…”