title: Association between CYP3A5 polymorphisms and blood pressure in kidney transplant recipients receiving calcineurin inhibitors.
abstract: Abstract   Renal cytochrome P450 3A5 (CYP3A5) has been associated with blood pressure (BP) control in humans. We investigated whether CYP3A5 polymorphisms are associated with post- transplant hypertension in a selected population of kidney recipients receiving calcineurin inhibitors.   Ninety-two kidney transplant recipients receiving cyclosporine (CyA) or tacrolimus (Tac) were genotyped for CYP3A5 polymorphisms, and the association between the CYP3A5 alleles (*1,*3) and hypertension on post-operative day (POD) 6 and POD 180 was verified, with multiple regression being used to identify the putative co-variates that may predict the extent and severity of hypertension in transplant recipients at different post-transplant times.   The CYP3A5*1 carriers had higher systolic (SBP) and diastolic blood pressure (DBP) in both the immediate and delayed post-transplant period when adjusted for anti-hypertensive medication (POD 6: SBP = 161 ± 23 vs. 140 ± 23 mmHg; DBP = 120 ± 15 vs. 87 ± 14 mmHg, p < 0.05. POD 180: SBP = 136 ± 16 vs. 129 ± 14 mmHg; DBP = 89 ± 15 vs. 80 ± 15 mmHg, p < 0.05). The severity of hypertension between the CYP3A5*1 carriers and noncarriers on POD 6 was documented by the significantly different distribution of hypertension classes, but this was not confirmed on POD 180. The CYP3A5 genotype was the only independent variable affecting mean arterial pressure.   The results of this study show that CYP3A5 polymorphisms are associated with the severity and degree of hypertension in kidney transplant recipients receiving calcineurin inhibitors regardless of the time of recording. However, the role of concomitant medications such as steroids with strong CYP3A5 inducing activity, should be taken into account.
authors.affiliation: Department of General Surgery, University of Milan Medical School, Saint Joseph Hospital, Milan, Italy. mariano.ferraresso@unimi.it
authors.forename: Mariano
authors.initials: M
authors.lastname: Ferraresso
authors.forename: Stefano
authors.initials: S
authors.lastname: Turolo
authors.forename: Luciana
authors.initials: L
authors.lastname: Ghio
authors.forename: Amedea S
authors.initials: AS
authors.lastname: Tirelli
authors.forename: Mirco
authors.initials: M
authors.lastname: Belingheri
authors.forename: Roberta
authors.initials: R
authors.lastname: Villa
authors.forename: Elena
authors.initials: E
authors.lastname: Groppali
authors.forename: Alberto
authors.initials: A
authors.lastname: Edefonti
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001794:Blood Pressure / Q000502:physiology*; D065095:Calcineurin Inhibitors; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D016030:Kidney Transplantation; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D012720:Severity of Illness Index; D016559:Tacrolimus / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D065095:Calcineurin Inhibitors; D016572:Cyclosporine; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus