CYP3A5 genotype is associated with longer patient survival after kidney transplantation and long-term treatment with cyclosporine.
The CYP3A5*1 allele has been linked to high expression of CYP3A5 and metabolism of cyclosporine. We evaluated the role of CYP3A5*1 for long-term survival in renal transplant patients in a cohort of 399 patients who underwent cadaveric or living donor kidney allograft transplantation. All patients were treated with a similar cyclosporine-based immunosuppressive maintenance therapy protocol. The mean duration of follow-up was 8.6+/-3.7 years. In univariate survival analysis, the presence of the CYP3A5*1 allele in recipients significantly increased patient survival P=0.028 (log-rank), resulting in a hazard ratio (HR) of 0.52 (95% CI=0.29-0.94). When the presence of the CYP3A5*1 allele was included in multivariate Cox regression analyses accounting for major risk factors for patient death, CYP3A5*1 still conferred a protective effect. Further, haplotype analysis at the CYP3A5 locus confirmed that CYP3A5*1 might indeed be responsible for this survival benefit.
Kreutz
R
R
Department of Clinical Pharmacology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany. reinhold.kreutz@charite.de
Bolbrinker
J
J
van der Sman-de Beer
F
F
Boeschoten
E W
EW
Dekker
F W
FW
Kain
S
S
Martus
P
P
Sietmann
A
A
Friedrichs
F
F
Stoll
M
M
Offermann
G
G
Beige
J
J
D015331:Cohort Studies; D016572:Cyclosporine / Q000627:therapeutic use*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation; D016019:Survival Analysis
D007166:Immunosuppressive Agents; D016572:Cyclosporine; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A