Investigation of the Genetic Link Between the Metabolic Diseases Gout and Type 2 Diabetes

-------------------------------------------------------------------------------------------------------------------------II ACKNOWLEDGEMENTS --------------------------------------------------------------------------------------------------------IV TABLE OF CONTENTS -------------------------------------------------------------------------------------------------------------V LIST OF FIGURES -----------------------------------------------------------------------------------------------------------------XII LIST OF TABLES ------------------------------------------------------------------------------------------------------------------XVI ABBREVIATIONS ----------------------------------------------------------------------------------------------------------------XIX CHAPTER 1: INTRODUCTION-------------------------------------------------------------------------------------------------1 GENETICS OF COMPLEX DISEASES ---------------------------------------------------------------------------------------------------2 Approaches to gene mapping -------------------------------------------------------------------------------------------------------2 GOUT ---------------------------------------------------------------------------------------------------------------------------------4 1.1Brief history of gout --------------------------------------------------------------------------------------------------------------5 1.2Epidemiology of gout ------------------------------------------------------------------------------------------------------------6 1.3Synthesis of uric acid in the body ---------------------------------------------------------------------------------------------8 1.4Loss of uricase---------------------------------------------------------------------------------------------------------------------10 1.5Urate transport in the kidney -------------------------------------------------------------------------------------------------11 1.6Stages of gout ---------------------------------------------------------------------------------------------------------------------14 1.7Uric acid crystals and inflammation ----------------------------------------------------------------------------------------17 1.8Risk factors for gout -------------------------------------------------------------------------------------------------------------19 1.9Role of genetics in the development of hyperuricaemia and gout --------------------------------------------------23 1.10Treatment of gout --------------------------------------------------------------------------------------------------------------28 1.11Complications of gout ---------------------------------------------------------------------------------------------------------32 TYPE 2 DIABETES -------------------------------------------------------------------------------------------------------------------33 1.12Control of blood glucose ------------------------------------------------------------------------------------------------------33 1.13Epidemiology of type 2 diabetes worldwide ----------------------------------------------------------------------------34 1.14Pathophysiology of type 2 diabetes ---------------------------------------------------------------------------------------36 1.15Risk factors for type 2 diabetes ---------------------------------------------------------------------------------------------39 1.16Genetics of type 2 diabetes --------------------------------------------------------------------------------------------------43