The prevalence of chronic kidney disease is rising sharply worldwide and affects 13.1% of the population in the USA. Hypertension is one of the major causes of renal injury. Low-grade inflammation is associated with cardiovascular disease and specifically with hypertension. Inflammation and oxidative stress are major mediators in the development and progression of renal disease. There is increasing evidence that genetic factors contribute to the susceptibility to renal disease associated with hypertension and it has been suggested that hypertension may cause progressive kidney disease only in genetically susceptible individuals. The genetic predisposition to chronic kidney disease is polygenic but so far only a few genes have been shown to be contributory. This project will test the overall novel hypothesis that the dopamine D2 receptor regulates the inflammatory reaction in the kidney and that impaired function of the D2 receptor results in renal inflammation and end-organ damage. Polymorphisms of the D2 receptor gene are commonly observed in humans and some of them have been associated with elevated blood pressure and even hypertension. Several polymorphisms of the D2 receptor result in decreased expression/function of the receptor. If our hypothesis proves to be correct, then individuals carrying these polymorphisms could be more vulnerable to renal injury when challenged with an insult such as elevated blood pressure. These results could then be critical for designing innovative genetic testing assays and therapeutics.
Genetic factors contribute to the susceptibility to renal disease associated with essential hypertension. Inflammation is crucial in the development of renal injury. This project will test the overall novel hypothesis that impaired function of the dopamine D2 receptor results in renal inflammation and end-organ damage. Several polymorphisms of the D2 receptor result in decreased expression of the receptor or decreased receptor affinity. If our hypothesis proves to be correct, then individuals carrying these polymorphisms could be more vulnerable to renal injury.
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