RGD Reference Report - ABCB1 genotypes predict cyclosporine-related adverse events and kidney allograft outcome. - Rat Genome Database

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ABCB1 genotypes predict cyclosporine-related adverse events and kidney allograft outcome.

Authors: Cattaneo, D  Ruggenenti, P  Baldelli, S  Motterlini, N  Gotti, E  Sandrini, S  Salvadori, M  Segoloni, G  Rigotti, P  Donati, D  Perico, N  Remuzzi, G  Remuzzi, Giuseppe 
Citation: Cattaneo D, etal., J Am Soc Nephrol. 2009 Jun;20(6):1404-15. Epub 2009 May 21.
RGD ID: 2312331
Pubmed: PMID:19470683   (View Abstract at PubMed)
PMCID: PMC2689900   (View Article at PubMed Central)
DOI: DOI:10.1681/ASN.2008080819   (Journal Full-text)

Cyclosporine A (CsA) is a substrate of P-glycoprotein, an efflux transporter encoded by the ABCB1 gene. Compared with carriers of the wild-type gene, carriers of T allelic variants in exons 21 or 26 have reduced P-glycoprotein activity and, secondarily, increased intracellular concentration of CsA; therefore, carriers of T variants might be at increased risk for CsA-related adverse events. We evaluated the associations between ABCB1 genotypes (in exons 12, 21, and 26) and CsA-related outcomes in 147 renal transplant recipients who were receiving CsA-based immunosuppression and were included in the Mycophenolate Steroids Sparing study. During a median of 65.5 mo follow-up, carriers of T allelic variants in exons 21 or 26 had a three-fold risk for delayed graft function (DGF), a trend to slower recovery of renal function and lower GFR at study end, and significantly higher incidences of new-onset diabetes and cytomegalovirus reactivation compared with carriers of the wild-type genotype. T variants in both exons 21 and 26 were independently associated with 3.8- and 3.5-fold higher risk for DGF, respectively (P = 0.022 and P = 0.034). The incidence of acute rejection and the mean CsA dose and blood levels were comparable in genotype groups. In conclusion, renal transplant recipients with T allelic variants in ABCB1 exons 21 or 26 are at increased risk for CsA-related adverse events. Genetic evaluation may help to identify patients at risk and to modulate CsA therapy to optimize graft and patient outcomes.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
type 2 diabetes mellitus  IAGP 2312331DNA:polymorphism:exon (human)RGD 
type 2 diabetes mellitus  ISOABCB1 (Homo sapiens)2312331DNA:polymorphism:exon (human)RGD 
type 2 diabetes mellitus  ISO2312331DNA:polymorphism:exon (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Abcb1a  (ATP binding cassette subfamily B member 1A)

Genes (Mus musculus)
Abcb1a  (ATP-binding cassette, sub-family B member 1A)

Genes (Homo sapiens)
ABCB1  (ATP binding cassette subfamily B member 1)


Additional Information