Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumour necrosis factor (TNF) alpha is involved in the pathogenesis of established lymphoproliferative disease. Serum levels of TNFalpha and its soluble receptors are above normal values in B-cell chronic lymphocytic leukaemia (B-CLL) and they are valuable prognostic markers in lymphoma patients. The production of TNFalpha is genetically controlled. Altered synthesis of TNFalpha has been associated with polymorphisms at the TNF gene cluster (i.e. TNFA, TNFB and LTB). In the present study, we evaluated the prevalence of the known high TNFalpha- and TNFbeta- producing alleles TNF1, TNF2 of the TNFA gene, TNFB1, TNFB2 alleles of the TNFB gene and of the polymorphic alleles TNFd1, d2, d3, d4 and d5 of the microsatellite TNFd in patients with B-CLL, non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD). This study demonstrates that there is no difference in the frequency of the tested TNF alleles between normal controls and cohorts of patients with lymphoproliferative disease. These results indicate that TNF alleles are not genetic predisposing factors in the development of these diseases.
 ...
PMID:Tumour necrosis factor gene polymorphisms in lymphoproliferative disease. 1095 76

In the previous studies, some human major histocompatibility complex (MHC) genes such as TNF, LTA and human leukocyte antigen (HLA)-DR2 genes and A1-B8-TNF(-308A) haplotype were implied in non-Hodgkin's lymphoma (NHL) outcome. In the current study, we have assigned most probable six-locus haplotypes determined by HLA-A, -Cw, -B and -DRB1 highly polymorphic genes and non-HLA LTA(+252) and TNF(-308) single nucleotide polymorphisms (SNPs) in 152 NHL Caucasian French patients. We have broadly mapped the MHC region by its component blocks and tagging alleles. Ten frequent (with haplotype frequency >1%) six-locus extended haplotypes (EHs) were revealed in NHL patients. The only two adjacent locus fragment of 8.1 EH associated with shortened freedom from progression (FFP) was B*08-LTA(+252G) (P= 0.0084, RR = 2.45). Interestingly, 305-kbp-long, four-locus fragment of 8.1 EH, Cw*07-B*08-LTA(+252G)-TNF(-308A) block was much strongly associated with shortened FFP (P= 0.00045, RR = 3.26). The analysis of further extended haploblocks comprising five or six loci showed weaker association with outcome measures, suggesting linkage disequilibrium to be the cause of DRB1*03 and A*01 allele associations. In contrast, all fragments of 7.1 EH influenced FFP favorably with top association of TNF(-308G) allele. In multivariate analysis, only Cw*07-B*08-LTA(+252G)-TNF(-308A) and TNF(-308G)-DRB1*01 haplotypes remained predictive for shortened FFP (P= 0.024 and 0.027, respectively) and independent of International Prognostic Index (P= 0.00044). This study reveals that the block composition of EHs may cause important functional differences for NHL outcomes. Further study will be required in NHL patients by fine mapping with dense microsatellite or SNP tags to define susceptibility genes in associating regions.
 ...
PMID:Haplotype-specific pattern of association of human major histocompatibility complex with non-Hodgkin's lymphoma outcome. 1797 Oct 52