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