1. Association of chronic lymphocytic leukemia with specific alleles of the HLA-DR4:DR53:DQ8 haplotype in German patients
- Author
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H K, Machulla, L P, Müller, A, Schaaf, G, Kujat, U, Schönermarck, and J, Langner
- Subjects
Male ,HLA-DP Antigens ,Genetic Linkage ,Histocompatibility Testing ,Homozygote ,HLA-DR Antigens ,Middle Aged ,Leukemia, Lymphocytic, Chronic, B-Cell ,Gene Frequency ,Haplotypes ,Germany ,HLA-DQ Antigens ,HLA-DR4 Antigen ,Humans ,Female ,Alleles ,HLA-DP beta-Chains ,HLA-DRB4 Chains - Abstract
The etiology of chronic lymphocytic leukemia (CLL) remains unknown, though a genetic susceptibility has been suggested. Results of complete DNA typing of HLA alleles in CLL patients are lacking. We compared HLA class I and class II frequencies in 101 German CLL patients and 157 healthy German controls as determined by PCR-SSP/SSO DNA analysis and serologic typing. The most striking difference was the increased frequency of HLA-DRB4*0103 [relative risk (RR) = 2.74, p0.0025] among patients. The presence of alleles HLA-DRB1*0401, HLA-DQB1*0302 and HLA-DPB1*0301 as well as of homozygosity for HLA-DQB1 was also associated with a higher risk for CLL, though none of these differences remained significant after correction for multiple comparisons. No association was found for any HLA class I allele. Haplotype analysis revealed a CLL-specific linkage disequilibrium for HLA-DRB1*0401:DRB4*0103 and HLA-DRB4*0103:DQB1*0302. Our results suggest that CLL could be associated with distinct class II alleles of the Caucasian haplotype HLA-DR4:DR53:DQ8, which has also been related to a susceptibility for several auto-immune diseases. The positive, though weak, association of CLL with HLA-DPB1*0301 might represent an independent susceptibility factor since no linkage disequilibrium existed with any of the other CLL-associated alleles. None of the previously reported associations with HLA class I antigens was confirmed. Our results suggest that factors within or close to the human MHC class II region confer susceptibility to CLL.
- Published
- 2001