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Haplotype-specific pattern of association of human major histocompatibility complex with non-Hodgkin's lymphoma outcome.
- Source :
-
Tissue antigens [Tissue Antigens] 2008 Jan; Vol. 71 (1), pp. 16-26. Date of Electronic Publication: 2007 Oct 29. - Publication Year :
- 2008
-
Abstract
- 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.
- Subjects :
- Alleles
Case-Control Studies
Female
Genetic Predisposition to Disease
HLA-A Antigens genetics
HLA-A1 Antigen
HLA-B Antigens genetics
HLA-B8 Antigen
HLA-D Antigens immunology
HLA-DR Antigens genetics
Histocompatibility Antigens Class I immunology
Histocompatibility Antigens Class II immunology
Humans
Lymphoma, Non-Hodgkin immunology
Lymphoma, Non-Hodgkin mortality
Male
Middle Aged
Prognosis
Prospective Studies
HLA-D Antigens genetics
Haplotypes immunology
Histocompatibility Antigens Class I genetics
Histocompatibility Antigens Class II genetics
Lymphoma, Non-Hodgkin genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0001-2815
- Volume :
- 71
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Tissue antigens
- Publication Type :
- Academic Journal
- Accession number :
- 17971052
- Full Text :
- https://doi.org/10.1111/j.1399-0039.2007.00954.x