Relationship between TNFA, TNFB and TNFRII gene polymorphisms and outcome after unrelated hematopoietic cell transplantation in a Chinese population

Abstract

This study aimed to analyze the association between cytokine gene polymorphisms and outcome following allogeneic hematopoietic SCT (allo-HSCT). A total of 138 unrelated donor/recipient pairs who underwent allo-HSCT from 2001 to 2009 were tested for TNFA-1031 (T4C), -863 (C4A), -857 (C4T), -238 (G4A), TNFB þ 252 (A4G) and TNFRII codon 196 (T4G) single nucleotide polymorphisms by multiplex SnaPshot analysis. Transplantation involving recipients and/or donors with TNFA-857 C/C genotype or TNFB þ 252 G allele-positivity resulted in a higher incidence of acute GVHD (aGVHD), which was independent of HLA mismatching. In multivariate analysis, TNFA-857 C/C genotype donors (relative risk (RR) ¼ 2.29, P ¼ 0.006) and TNFB þ 252 G allele-positive recipients (RR ¼ 1.789, P ¼ 0.036) were found to be significantly associated with an increased incidence of aGVHD. TNFA-857 C/C genotype donors (RR ¼ 3.748, P ¼ 0.002) and TNFB þ 252 G allele-positive recipients (RR ¼ 1.823, P ¼ 0.063) were also associated with the development of grades II-IV aGVHD. TNFRII polymorphism in recipients was also related to relapse rate, but no significant associations were found between TNFA, TNFB or TNFRII 196 genotype and cGVHD, relapse or overall survival after transplantation. These results provide the first report of an association between TNFA, TNFB and TNFRII polymorphic features and outcome of allo-HSCT in a Chinese population, and suggest an interaction between TNFA-857 and TNFB þ 252 genotypes and risk of aGVHD.

Combining therapeutic antibodies using basiliximab and etanercept for severe steroid-refractory acute graft-versus-host disease: A multi-center prospective study

“…Acute GVHD involved skin in 54 patients, gut in 59 patients, and liver in 42 patients. The median number of infusions of basiliximab was 4 (range [2][3][4][5][6][7][8][9][10][11], and the median number of etanercept was 9 (range 2-12). At day 28 after the initiation of treatment with the combination of basiliximab and etanercept, the overall response rate (ORR) (CRCPR) to second-line treatment was 90.8% (59/65) including 49 CRs (75.4%).…”

“…[6][7][8] Mono-therapy targeting T-cell activation by IL-2R antibody (basiliximab) [9][10][11] or single drug using TNF-a antagonisms (infliximab, etanercept) 12,13 has shown encouraging results in smaller, retrospective studies of patients with SRaGVHD. We hypothesized that the simultaneous blockade of activated T cells and pivotal cytokines may further improve the outcomes of patients with SR-aGVHD.…”

Donor TLR9 gene tagSNPs influence susceptibility to aGVHD and CMV reactivation in the allo-HSCT setting without polymorphisms in the TLR4 and NOD2 genes

“…This strategy identified 10 SNPs in the TLR1 gene ( þ 743 C/T, rs4833095; À 216A/G, rs5743565), TLR2 gene (-2098A/C, rs11938228; þ 597 C/T, rs3804099), TLR3 gene ( þ 1234A/G, rs3775291; À 7G/T, rs3775296), TLR8 gene ( þ 1A/G, rs3764880; þ 354 C/T, rs2159377) and TLR9 gene ( þ 1174A/G, rs352139; þ 1635 C/T, rs352140). SNP genotype was determined using multiplex SNaPshot technology, according to previously described methods [15][16][17] with the help of an ABI fluorescencebased allelic discrimination method assay (Applied Biosystems, Foster City, CA, USA). The detailed information of primers is available in Supplementary Methods (Supplementary Table S1).…”

Clinical significance of SOD2 and GSTP1 gene polymorphisms in Chinese patients with gastric cancer

“…15 The SOD2 (rs4880) and GSTP1 (rs1695) SNPs were examined by multiplex SNaPshot technology using an ABI fluorescence-based assay allelic discrimination method (Applied Biosystems, Foster City, Calif) as described previously. 16 The primers were designed to anneal immediately adjacent to the nucleotide at the mutation site: SOD2 rs4880: forward, 5…”