Donor gene clue to kidney transplant rejection

Genetic study results show that long-term kidney transplant rejection risk may be increased if the organ donor has a variant form of the multidrug resistance 1 (MDR1) gene.

Donors with the CC genotype had a 69% higher risk for kidney transplant rejection than those with non-CC genotypes, explain Richard Borrows (University Hospital Birmingham, UK) and co-authors.

Given that the MDR1 gene is integral to renal processing of immunosuppressive drugs that reduce transplant rejection risk, this is an area that requires additional investigation, say the authors.

They add: "This gene variant certainly represents a promising candidate for future genetic studies in kidney transplantation."

The findings, published in the Journal of the American Society of Nephrology, arise from the analysis of genetic material taken from donors and recipients involved in 811 UK kidney transplant cases.

All kidney recipients were Caucasian, had a history of immunosuppressant therapy, and a mean age of 42.5 years.

Over a 163-month follow-up period, 79 kidney recipients died and 184 graft failures occurred.

The analysis of 52 single-nucleotide polymorphisms located in five genes (coding for proteins involved in the kidney transplant acceptance process) revealed that only the presence of a CC genotype for the C3435T variant of the MDR1 donor gene accurately predicted graft survival or mortality.

This genetic analysis was repeated in two independent cohorts consisting of 675 European and 2985 US Caucasian kidney donors with respective mean ages of 41.4 and 47.7 years.

The CC genotype was also found to be associated with an increased risk (68-84%) for transplant rejection in these two groups.

Borrows said in a press statement: "The study of donor, as opposed to recipient, gene variation is relatively uncommon in the field of transplantation, and it certainly warrants more attention."

The authors conclude: "Further long-term studies in contemporary cohorts, particularly in tacrolimus-treated patients, and in patients and donors of different racial backgrounds… are required to shed further light on the relationship between donor and recipient genotype and the important endpoints of renal transplantation."

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