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Reuters Health Information (2008-10-08): Genetic variant tied to pediatric liver transplant rejection


Genetic variant tied to pediatric liver transplant rejection

Last Updated: 2008-10-08 16:03:43 -0400 (Reuters Health)

NEW YORK (Reuters Health) - A single nucleotide polymorphism (SNP) in a major histocompatibility complex-linked gene appears to be associated with early liver transplant rejection in children, Pennsylvania-based researchers report in the September issue of Gastroenterology.

Dr. Rakesh Sindhi of the Children's Hospital of Pittsburgh and colleagues used microarrays to scan 1774 major histocompatibility complex SNPs in 240 DNA samples from 80 pediatric liver transplant patients and their biological parents.

The team then went on to compare 57 SNPs with large differences in minor allele frequencies in the 37 children who had experienced early rejection (rejectors) and the remaining 43 who had not.

The researchers ultimately established that the minor allele G of the SNP rs9296068 near HLA-DOA was significantly associated with liver transplantation rejection.

"Also, intragraft B lymphocytes, whose antigen-presenting function is selectively inhibited by HLA-DOA, were 3-fold more numerous during rejection among rejectors with the risk allele, than those without," the team found.

The multi-step technique employed, say the investigators, "identifies the HLA-DOA gene, and the B-lymphocyte in which it is exclusively expressed, as plausible candidates contributing to pediatric liver transplant rejection."

Commenting on the findings, Dr. Sindhi told Reuters Health, "Our approach to developing predictive markers with multi-layered genetic scanning tells us that rare but complex diseases can also be understood as well as more common illnesses such as diabetes."

Gastroenterology 2008;135:830-839.

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