Xanthine oxidase gene variants and their association with blood pressure and incident hypertension

Scheepers, Lieke E.J.M.; Wei, Fang; Stolarz‐Skrzypek, Katarzyna; Malyutina, Sofia; Tikhonoff, Valérie; Thijs, Lutgarde; Salvi, Erika; Barlassina, Cristina; Filipovský, Jan; Casíglia, Edoardo; Nikitin, Yu. P.; Kawecka‐Jaszcz, Kalina; Manunta, Paolo; Cusi, Daniele; Boonen, Annelies; Staessen, Jan A.; Arts, Ilja C. W.

doi:10.1097/hjh.0000000000001077

Cited by 33 publications

(21 citation statements)

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“…However the studies were limited in size and careful meta-analyses may be warranted (reviewed in ( 170 )). This question of whether XO inhibitors have potential therapeutic benefit in cardiovascular disease, has been the subject of a number of clinical investigations ( 175 , 180 – 183 ). However, the impact of early intervention in patients with asymptomatic hyperuricemia (with or without crystal deposition) on vascular outcomes has not been definitively demonstrated ( 184 ).…”

Section: Epidemiology Of Hyperuricemia and Associated Comorbiditiesmentioning

confidence: 99%

Physiology of Hyperuricemia and Urate-Lowering Treatments

et al. 2018

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Gout is the most common form of inflammatory arthritis and is a multifactorial disease typically characterized by hyperuricemia and monosodium urate crystal deposition predominantly in, but not limited to, the joints and the urinary tract. The prevalence of gout and hyperuricemia has increased in developed countries over the past two decades and research into the area has become progressively more active. We review the current field of knowledge with emphasis on active areas of hyperuricemia research including the underlying physiology, genetics and epidemiology, with a focus on studies which suggest association of hyperuricemia with common comorbidities including cardiovascular disease, renal insufficiency, metabolic syndrome and diabetes. Finally, we discuss current therapies and emerging drug discovery efforts aimed at delivering an optimized clinical treatment strategy.

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Section: Epidemiology Of Hyperuricemia and Associated Comorbiditiesmentioning

confidence: 99%

Physiology of Hyperuricemia and Urate-Lowering Treatments

et al. 2018

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“…Increased XO activity, rather than SUA, could be responsible for an adverse cardiovascular outcome. In line with this hypothesis, a recent study examined several XO gene variants in a prospective cohort of 2500 European participants and found three minor alleles associated with increased risk of hypertension [77]. Despite the enzymatic activity controlled by these variants being uncertain, another a longitudinal cohort study of 246 Dutch children (mean age 7 years) [78], led by the same investigator, showed that XO activity, estimated by a ratio of purine to uric acid, was associated with blood pressure.…”

Section: Hyperuricaemia and Cardiovascular And Renal Diseasesmentioning

confidence: 99%

Impact of comorbidities on gout and hyperuricaemia: an update on prevalence and treatment options

Bardin

Richette

2017

BMC Med

274

159

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Gout, the most prevalent inflammatory arthritis worldwide, is associated with cardiovascular and renal diseases, and is an independent predictor of premature death. The frequencies of obesity, chronic kidney disease (CKD), hypertension, type 2 diabetes, dyslipidaemias, cardiac diseases (including coronary heart disease, heart failure and atrial fibrillation), stroke and peripheral arterial disease have been repeatedly shown to be increased in gout. Therefore, the screening and care of these comorbidities as well as of cardiovascular risk factors are of outmost importance in patients with gout. Comorbidities, especially CKD, and drugs prescribed for their treatment, also impact gout management. Numerous epidemiological studies have shown the association of asymptomatic hyperuricaemia with the above-mentioned diseases and cardiovascular risk factors. Animal studies have also produced a mechanistic approach to the vascular toxicity of soluble urate. However, causality remains uncertain because confounders, reverse causality or common etiological factors might explain the epidemiological results. Additionally, these uncertainties remain unsolved despite recent studies using Mendelian randomisation or therapeutic approaches. Thus, large randomised placebo-controlled trials are still needed to assess the benefits of treating asymptomatic hyperuricaemia.

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“…These results contrast with Mendelian randomization studies that have examined genetic polymorphisms involved in the renal handling of uric acid and that suggest these genes most likely do not directly increase the risk of cardiovascular disease [9]. More recent studies have investigated the relevance of genetic polymorphisms affecting xanthine oxidoreductase (XOR)-activity, with disparate conclusions [10,11].…”

Section: Introductionmentioning

confidence: 81%

Uric acid and hypertension

Becker

Borghi

Burnier

et al. 2019

Journal of Hypertension

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Uric acid levels are higher in humans than in other mammals. Best known as an extracellular antioxidant, uric acid also increases salt sensitivity, fat storage, and lipogenesis. Xanthine oxidase-related oxidative stress may also induce endothelial dysfunction and renal vasoconstriction. Renal structure abnormalities contribute to salt-sensitive and uric acid-independent hypertension. Maternal hyperuricemia during pregnancy and hyperuricemia early in life are likewise independent risk factors for hypertension. Genetic polymorphism is potentially involved in the activity of xanthine oxidoreductase, but further studies are needed. Xanthine oxidase inhibition consistently decreases blood pressure in younger hypertensive patients, albeit modestly. Hyperuricemia affects one out of five adults as a result of the Western diet, insulin resistance, and renal dysfunction. This review advocates lifestyle changes to maintain uric acid levels within the normal range in young (pre)hypertensive individuals or normotensives with a family history of hypertension, metabolic disorders, or obesity; moreover, antihypertensive medications that increase uric acid levels should be avoided.

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Xanthine oxidase gene variants and their association with blood pressure and incident hypertension

Abstract: Pending confirmation, our findings suggest that variation in uric acid production, as captured by genetic variation in XOR, might be a predictor of changes in BP and in the risk of hypertension.

Cited by 33 publications

References 50 publications

Physiology of Hyperuricemia and Urate-Lowering Treatments

Physiology of Hyperuricemia and Urate-Lowering Treatments

Impact of comorbidities on gout and hyperuricaemia: an update on prevalence and treatment options

Uric acid and hypertension

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