Thrombospondin-1 polymorphisms influence risk of corneal allograft rejection.

Purpose: We investigated single nucleotide polymorphisms (SNPs) of thrombospondin-1 (TSP-1) on the risk of corneal allograft rejection. The TSP-1 is known to be involved in the immune response of the anterior chamber of the eye, activating TGF-β2, promoting peripheral and systemic tolerance, and counteracting the proangiogenic activity of VEGF.

Methods: Three tagging SNPs spanning the TSP-1 region (rs1478604, A>G; rs2228261, C>T; and rs2228262, A>G) were genotyped.

Relationship between vascular endothelial growth factor + 936 genotype and plasma/epithelial lining fluid vascular endothelial growth factor protein levels in patients with and at risk for ARDS.

Background: Vascular endothelial growth factor (VEGF) is postulated to have a role in ARDS. The functional VEGF + 936 polymorphic T allele is associated with an increased susceptibility to and severity of ARDS. The reasons for this are unclear.

Haplotypic structure across the I kappa B alpha gene (NFKBIA) and association with multiple myeloma.

Polymorphisms in NFKBIA may be important in pre-disposition to and outcome after treatment, of multiple myeloma (MM). The NFKBIA gene product, IkappaBalpha, binds to NF-kappaB preventing its activation and is important in mediating resistance to apoptosis in B-cell lymphoproliferative diseases. This study investigates eight polymorphisms across the NFKBIA gene in large patient and control populations.

Haplotypes in the tumour necrosis factor region and myeloma.

This study described the haplotypic structure across a region of chromosome 6 including the tumour necrosis factor (TNF) gene, and investigated its influence on the aetiology of myeloma. A total of 181 myeloma cases from the Medical Research Council Myeloma VII trial and 233 controls from the Leukaemia Research Fund Case Control Study of Adult Acute Leukaemia were included in the analysis. Genotyping by induced heteroduplex generator analysis was carried out for single nucleotide polymorphisms (SNP) located at positions -1031, -863, -857, -308 and -238 of the 5' promoter region of TNF-alpha gene, and 252 in the LT-alpha gene; and five microsatellites, TNFa, b, c, d and e.

Patient interleukin-18 GCG haplotype associates with improved survival and decreased transplant-related mortality after unrelated-donor bone marrow transplantation.

Interleukin-18 (IL-18), a proinflammatory cytokine, is elevated in patients with acute graft-versus-host disease (aGVHD). IL-18 induces Th1 differentiation and cytotoxic T-lymphocyte function, both of which have been implicated in the pathogenesis of aGVHD. However, recent studies have shown that neutralization of IL-18 by antibodies leads to an increased risk of aGVHD-related mortality while administration of IL-18 significantly improved survival.

Interleukin-10 and tumor necrosis factor alpha region haplotypes predict transplant-related mortality after unrelated donor stem cell transplantation.

Certain cytokine gene polymorphisms have been shown to correlate with outcome of human leukocyte antigen (HLA) identical sibling donor stem cell transplantation (SCT), but in unrelated donor SCT such information is scarce. We have studied the association between cytokine gene polymorphism and transplant-related mortality (TRM) in 182 unrelated SCTs performed at a single center. We found association of polymorphism in the tumor necrosis factor alpha (TNF alpha) and interleukin-10 (IL-10) gene and TRM.