No association between single nucleotide polymorphisms and the development of nephrotoxicity after orthotopic heart transplantation.
BACKGROUND
Survival for heart transplantation (HTx) patients is limited by nephrotoxicity of the calcineurin inhibitors cyclosporine and tacrolimus. To determine whether genetic factors are involved in the development of renal dysfunction under immunosuppressive therapy, we screened various genes for sequence variations.


METHODS
In a case-control study we analyzed in parallel polymorphisms within the transforming growth factor-beta1 gene (TGF-beta1; L10P, R25P), the multidrug resistance gene MDR 1 (A893T/S) and the CYP3A5 gene (CYP3A5*1/*3 allele). In total, we included 53 cardiac allograft recipients with renal insufficiency (serum creatinine >or=1.8 mg/dl and glomerular filtration rate <50 ml/min/1.73 m(2)) and 53 patients with normal renal function as controls. The controls were matched with patients for age, gender and post-HTx time. The polymorphisms were assessed by denaturing high-performance liquid chromatography (dHPLC) and direct sequencing. We performed univariate and multivariate logistic regression analysis to assess the association between different gene variants and renal dysfunction.


RESULTS
No significant (p > 0.05) relationship was found between the polymorphisms investigated and the susceptibility of renal insufficiency under immunosuppressive therapy.


CONCLUSIONS
Our data do not justify genotyping of the investigated single nucleotide polymorphisms (SNPs) to assess the development of renal dysfunction post-HTx.
Klauke
Bärbel
B
Heart- and Diabetescenter NRW, Universitätsklinikum der Ruhr Universität Bochum, Erich and Hanna Klessmann Institut für Kardiovaskuläre Forschung and Entwicklung, Bad Oeynhausen, Germany.
Wirth
Andreas
A
Zittermann
Armin
A
Bohms
Birte
B
Tenderich
Gero
G
Körfer
Reiner
R
Milting
Hendrik
H
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000328:Adult; D016022:Case-Control Studies; D016572:Cyclosporine / Q000009:adverse effects; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D005260:Female; D005838:Genotype; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D051437:Renal Insufficiency / Q000139:chemically induced* / Q000235:genetics*; D016559:Tacrolimus / Q000009:adverse effects; D053773:Transforming Growth Factor beta1 / Q000235:genetics
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; D053773:Transforming Growth Factor beta1; D016572:Cyclosporine; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus