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Revisiting the role of uric acid on cardiovascular risk using genetic and classical epidemiological approaches

English title Revisiting the role of uric acid on cardiovascular risk using genetic and classical epidemiological approaches
Applicant Bochud Murielle
Number 127393
Funding scheme ProDoc
Research institution Institut Universitaire de Médecine Sociale et Préventive - IUMSP CHUV et Université de Lausanne
Institution of higher education University of Lausanne - LA
Main discipline Cardiovascular Diseases
Start/End 01.05.2010 - 30.04.2013
Approved amount 154'583.00
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All Disciplines (2)

Discipline
Cardiovascular Diseases
Methods of Epidemiology and Preventive Medicine

Keywords (5)

genetic epidemiology; hypertension; metabolic syndrome; cardiovascular disease; primary prevention

Lay Summary (English)

Lead
Lay summary
Hypertension affects about 1 billion individuals worldwide. Many studies have shown that hypertension is associated with increased levels of uric acid in blood (hyperuricemia). Increasing observational and experimental evidence in animals and in humans supports a causal role of hyperuricemia in hypertension.

Hyperuricemia is a feature of the metabolic syndrome, which represents a clustering of cardiovascular risk factors. A high fructose intake (e.g. through consumption of soft drinks and other foods sweetened with corn syrup, which is increasingly produced at world level) has been shown to increase serum uric acid levels. Serum uric acid level is highly heritable and numerous genes have been identified so far. We plan to use genetic variant association with serum uric acid levels to explore the causal role of uric acid on hypertension using a new method called "Mendelian randomization".

The research project will address the following research questions:
1. Does a Mendelian randomization approach allow inferring causal relationships between serum uric acid, on one hand, and blood pressure and renal function, on the other hand? This hypothesis will be examined using genetic variants in the SCL2A9 gene in the population-based CoLaus study. This analysis can be extended to other genes recently identified as associated with serum uric acid.
2. Are there ethnic differences in the association between serum uric acid and cardiovascular risk factor clustering? This hypothesis will be examined in the data from the Colaus Study (n>5000, mostly Caucasian descent) and population-based surveys in the Seychelles (n>2200, mostly African descent).
3. Systematic review (meta-analysis or narrative) of the relationship between fructose intake and serum uric acid.
4. What study design is most suitable to explore the blood pressure lowering effect of the uric acid lowering drug, allopurinol, in the Swiss and the Seychelles' contexts? This will include ad hoc protocol writing.

The planned research project will help clarify the causal relationship between uric acid, on the one side, and hypertension and other metabolic traits, on the other side. Considering the very high disease burden associated with hypertension worldwide, drugs that lower serum uric acid may represent a promising new therapeutic approach to treat hypertension. Preventive measures, such as reduced fructose intake as a means to decrease uric acid production, could represent novel strategies for the primary prevention of hypertension and related cardiovascular morbidity and mortality. This topic has therefore high relevance from both pathophysiological and public health perspectives.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Blood pressure and cognitive function: a prospective analysis among adolescents in Seychelles
Lyngdoh Tanica, Viswanathan B, Kobrosly R, van Wijngaarden E, Huber B, Davidson PW, Cory-Slechta DA, Strain S, Myers GJ, Bovet Pascal (2013), Blood pressure and cognitive function: a prospective analysis among adolescents in Seychelles, in Journal of Hypertension, 31(6), 1175-1182.
Serum uric Acid and adiposity: deciphering causality using a bidirectional mendelian randomization approach.
Lyngdoh Tanica, Vuistiner Philippe, Marques-Vidal Pedro, Rousson Valentin, Waeber Gérard, Vollenweider Peter, Bochud Murielle (2012), Serum uric Acid and adiposity: deciphering causality using a bidirectional mendelian randomization approach., in PloS one, 7(6), 39321-39321.
Elevated serum uric acid is associated with high circulating inflammatory cytokines in the population-based Colaus study.
Lyngdoh Tanica, Marques-Vidal Pedro, Paccaud Fred, Preisig Martin, Waeber Gérard, Bochud Murielle, Vollenweider Peter (2011), Elevated serum uric acid is associated with high circulating inflammatory cytokines in the population-based Colaus study., in PloS one, 6(5), 19901-19901.
Association of statins with inflammatory cytokines: a population-based Colaus study.
Lyngdoh Tanica, Vollenweider Peter, Waeber Gérard, Marques-Vidal Pedro (2011), Association of statins with inflammatory cytokines: a population-based Colaus study., in Atherosclerosis, 219(1), 253-8.
Impact of different adiposity measures on the relation between serum uric acid and blood pressure in young adults.
Lyngdoh T, Viswanathan B, Myers G J, Bochud M, Bovet P (2011), Impact of different adiposity measures on the relation between serum uric acid and blood pressure in young adults., in Journal of human hypertension, x-x.

Collaboration

Group / person Country
Types of collaboration
Ministry of Health, Victoria Seychelles (Africa)
- Publication
Internal Medicine Department, CHUV, Lausanne Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
University of Rochester School of Medicine and Dentistry, Rochester, NY 14642 United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Swiss Society of Internal Medine Meeting 11.05.2011 Lausanne, Switzerland
EuroPrevent 14.04.2011 Geneva, Switzerland


Awards

Title Year
Best published PhD article in Pblic Health (2013) by the Swiss School of Public Health 2013

Associated projects

Number Title Start Funding scheme
119477 SSPH+ PhD Program in Public Health 01.10.2008 ProDoc
124087 Blood pressure and the kidney: interface between genes and environment 01.04.2009 SPUM

Abstract

Hypertension affects about 1 billion individuals worldwide. Many studies have shown that hypertension is associated with hyperuricemia. This association may be a consequence of reduced renal function, the use of diuretics, the presence of hyperinsulinemia and oxidative stress or elevated renal vascular resistance. However, increasing observational and experimental evidence in animals and in humans supports a causal role of hyperuricemia in hypertension. Hyperuricemia is a feature of the metabolic syndrome. A high fructose intake (e.g. through consumption of soft drinks and other foods sweetened with corn syrup, which is increasingly produced at world level) has been shown to increase serum uric acid levels. Serum uric acid level is highly heritable and numerous candidate genes have been identified so far, among which the solute carrier (SLC) family 2, member 9, gene (SLC2A9), a putative glucose transporter. Mendelian randomization, based on instrumental variables, can be used to infer causality using genetic data in observational epidemiology. When genetic variants explain a sufficient proportion of a trait variance, this genetically explained variance can be used to analyze associations with outcomes of interest (e.g. hypertension, decreased renal function, etc).The research project will address the following research questions:1.Does a Mendelian randomization approach allow inferring causal relationships between serum uric acid, on one hand, and blood pressure and renal function, on the other hand? This hypothesis will be examined using genetic variants located within and around the SCL2A9 gene among the sample of >5000 participants in the population-based CoLaus study. This analysis can be extended to other genes recently identified as associated with serum uric acid.2.Are there ethnic differences in the association between serum uric acid and cardiovascular risk factor clustering? This hypothesis will be examined in the data from the Colaus Study (n>5000, mostly Caucasian descent) and population-based surveys in the Seychelles (n>2200, mostly African descent).3.Systematic review (meta-analysis or narrative) of the relationship between fructose intake and serum uric acid. 4.What study design is most suitable to explore the blood pressure lowering effect of the uric acid lowering drug, allopurinol, in the Swiss and the Seychelles’ contexts? This will include ad hoc protocol writing.The proposed research module of the PhD programme will enable the PhD student to develop a large number of skills, such as (1) analyzing data, (2) writing research protocols and scientific papers, (3) summarizing the scientific literature and extract concise and meaningful available information and identify gaps in knowledge, (4) working independently, (5) interacting in an multidisciplinary team, (6) communicating and disseminating results, (7) managing administrative and other practical issues related to research projects. The planned research project will help clarify the causal relationship between uric acid, on the one side, and hypertension and other metabolic traits, on the other side. Considering the very high disease burden associated with hypertension worldwide, drugs that lower serum uric acid may represent a promising new therapeutic approach to treat hypertension. Preventive measures, such as reduced fructose intake as a means to decrease uric acid production, could represent novel strategies for the primary prevention of hypertension and related cardiovascular morbidity and mortality. This topic has therefore high relevance from both pathophysiological and public health perspectives.
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