Dataset Information

SULT genetic polymorphisms: physiological, pharmacological and clinical implications.

ABSTRACT:

Introduction

Cytosolic sulfotransferases (SULTs)-mediated sulfation is critically involved in the metabolism of key endogenous compounds, such as catecholamines and thyroid/steroid hormones, as well as a variety of drugs and other xenobiotics. Studies performed in the past three decades have yielded a good understanding about the enzymology of the SULTs and their structural biology, phylogenetic relationships, tissue/organ-specific/developmental expression, as well as the regulation of the SULT gene expression. An emerging area is related to the functional impact of the SULT genetic polymorphisms.

Areas covered

The current review aims to summarize our current knowledge about the above-mentioned aspects of the SULT research. An emphasis is on the information concerning the effects of the polymorphisms of the SULT genes on the functional activity of the SULT allozymes and the associated physiological, pharmacological, and clinical implications.

Expert opinion

Elucidation of how SULT SNPs may influence the drug-sulfating activity of SULT allozymes will help understand the differential drug metabolism and eventually aid in formulating personalized drug regimens. Moreover, the information concerning the differential sulfating activities of SULT allozymes toward endogenous compounds may allow for the development of strategies for mitigating anomalies in the metabolism of these endogenous compounds in individuals with certain SULT genotypes.

SUBMITTER: Kurogi K

PROVIDER: S-EPMC8369464 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAbnormal blood pressure (BP) responses to exercise can predict adverse cardiovascular outcomes, but their optimal measurement and definitions are poorly understood. We combined frequently sampled BP during cardiopulmonary exercise testing with vascular stiffness assessment to parse cardiac and vascular components of exercise BP.MethodsCardiopulmonary exercise testing with BP measured every two minutes and resting vascular tonometry were performed in 2858 Framingham Heart Study participants. Linear regression was used to analyze sex-specific exercise BP patterns as a function of arterial stiffness (carotid-femoral pulse wave velocity) and cardiac-peripheral performance (defined by peak O2 pulse).ResultsOur sample was balanced by sex (52% women) with mean age 54±9 years and 47% with hypertension. We observed variability in carotid-femoral pulse wave velocity and peak O2 pulse across individuals with clinically defined exercise hypertension (peak systolic BP [SBP] in men ≥210 mm Hg; in women ≥190 mm Hg). Despite similar resting SBP and cardiometabolic profiles, individuals with higher peak O2 pulse displayed higher peak SBP (P≤0.017) alongside higher fitness levels (P<0.001), suggesting that high peak exercise SBP in the context of high peak O2 pulse may in fact be favorable. Although both higher (favorable) O2 pulse and higher (adverse) arterial stiffness were associated with greater peak SBP (P<0.0001 for both), the magnitude of association of carotid-femoral pulse wave velocity with peak SBP was higher in women (sex-carotid-femoral pulse wave velocity interaction P<0.0001). In sex-specific models, exercise SBP measures accounting for workload (eg, SBP during unloaded exercise, SBP at 75 watts, and SBP/workload slope) were directly associated with the adverse features of greater arterial stiffness and lower peak O2 pulse.ConclusionsHigher peak exercise SBP reflects a complex trade-off between arterial stiffness and cardiac-peripheral performance that differs by sex. Studies of BP responses to exercise accounting for vascular and cardiac physiology may illuminate mechanisms of hypertension and clarify clinical interpretation of exercise BP.