Genetic susceptibility to adverse drug effects - Epidemiology ...

Contents
1. General introduction 11
2. Quantifying the risk of adverse drug reactions to digoxin
2. Age- and gender specific incidence of hospitalization for digoxin intoxication 19
3. Common variants in the ABCB1 gene
3.1 Common ABCB1 variants are associated with increased digoxin serum concentration
3.2 Common ABCB1 variants increase QTc shortening and risk of SCD in digoxin
users
3.3 ABCB1 (MDR1) gene polymorphisms are associated with neuropsychiatric adverse
effects of mefloquine
31
45
59
4 Common variants in the NOS1AP gene
4.1 Common NOS1AP variants are associated with a prolonged QTc interval in the
75
Rotterdam Study
4.2 Common NOS1AP variants potentiate digoxin induced QT-shortening and risk
89
of sudden cardiac death
4.3 Cardiovascular drugs, NOS1AP and QTc prolongation 103
4.4 Common variation in the NOS1AP gene is associated with reduced glucose lowering
effect and with increased mortality in users of sulfonylurea
119
5. Effect of ABCB1 and NOS1AP genotypes on cardiac function
5. Effect of ABCB1 and NOS1AP genotypes on cardiac function in digoxin users 135
6. General discussion 153
7. Summary
7.1 Summary 173
7.2 Samenvatting 177
8. Dankwoord 181
9. About the author 185
10. Bibliography 187