Saturday, October 13, 2012

Finding reveals cause for failure of transplanted organs

Organ transplantation has the potential to save people's lives. One of the major hurdles, in addition to actually acquiring the necessary organs, is rejection. That means the body rejects the transplanted organ because it is recognized as foreign, and therefore unwanted. Nowadays, we are able to suppress the acute form of rejection that is associated with organ transplantation, but chronic rejection, that develops over the course of many years, has proven to be a lot harder to get rid of. Patients have to take drugs that suppress the immune system to maintain usability of their newly acquired organ, something which is not beneficial for the body's ability to fight off infections. In the search of ways to improve organ compatibility, scientists stumbled upon a small genetic variant that may prove to be important for the success of a transplant.

Researchers from the University Hospital in Birmingham analysed genetic variety among patients that underwent a kidney transplantation, trying to link any changes they could find to the clinical outcome after the patients had received the organ. The variations that were studied were tiny: they included only a few genes and studied a total of 52 changes in individual building blocks. As genes can consist of millions of individual building blocks, it is peculiar that they can have such a marked effect on clinical outcomes. Such small modifications are called single nucleotide polymorphisms (or SNP), a nucleotide being a DNA building block and a polymorphism being a well-known site for variation.

Eventually, the scientists found that the variety in one particular building block for the ABCB1 gene was associated with altered survival of the transplanted kidney. ABCB1 provides the genetic instructions for a protein called MDR-1, which is an abbreviation for multi drug-resistant gene. Peculiar enough, this gene was previously found to be associated with drug resistance, hence the name, by transporting drug molecules across the cellular membrane and out of the cell.

Apparently, one of the polymorphisms found in ABCB1 is doing something quite important, as the variant was linked to a 69 percent increased risk of failure of the transplanted organ in the long run. So far, it is not known what explains this marked increase in risk of failure. Because the study encompassed a rather large number of patients, it is likely the researchers found something meaningful.

Due to our ever-increasing technological capabilities, recent years has seen the identification of many important genetic variants and their associated outcomes. Examples include variants that protect against parkinson's disease, a gene that promises higher intelligence, or how a gene can induce autism. Sadly, we have also found variants that reveal why conducting a successful transplantation is so cumbersome. To sum up, it is likely that we will discover many more genetic variants in the future, that contribute to our knowledge in the field of medicine.

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