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Gene Variant Increases Infection Risk After Transplant

Increased risk observed in transplant recipients from unrelated donors with the variant

WEDNESDAY, Oct. 22 (HealthDay News) -- A variant of a gene involved in the immune recognition of fungal pathogens increases the risk of invasive aspergillosis in recipients of a hematopoietic cell transplant when present in unrelated donors, according to an article published in the Oct. 23 issue of the New England Journal of Medicine.

Pierre-Yves Bochud, M.D., from the Institute for Systems Biology in Seattle, and colleagues examined the risk of invasive aspergillosis based on the presence of any of 20 single-nucleotide polymorphisms in the toll-like receptor (TLR) 2 (TLR2), TLR3, TLR4 and TLR9 genes in 336 hematopoietic cell transplant patients and their unrelated donors.

The researchers found a significantly higher risk of invasive aspergillosis in donors with two TLR4 haplotypes (adjusted hazard ratio 2.20 for haplotype S3, 6.16 for haplotype S4). The association of the S4 genotype was validated in an independent group of 103 case patients and 263 matched controls (adjusted odds ratio 2.49). The association was significant for unrelated recipients (OR, 5.00), but the association was not present for related recipients (OR, 2.29). Donors or recipients who were positive for cytomegalovirus, donors who were positive for the S4 haplotype, or both, had a significantly higher three-year likelihood of aspergillosis (12 versus 1 percent) and death unrelated to relapse (35 versus 22 percent), the report indicates.

"This study suggests an association between the donor TLR4 haplotype S4 and the risk of invasive aspergillosis among recipients of hematopoietic-cell transplants from unrelated donors," Bochud and colleagues conclude.

Authors of the study report financial relationships with the pharmaceutical industry.

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