Association of chronic lymphocytic leukemia with specific alleles of the HLA-DR4 : DR53 : DQ8 haplotype in German patients

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 cl ass II frequencies in 101 German CLL patients and 157 healthy German contro ls 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, P < 0.0025] among patients. The presence of alleles HLA- DRB 1*0401, HLA-DQB 1*0302 and HLA-DPB 1*0301 as well as of homozygosity fo r HLA-DQB1 was also associated with a higher risk for CLL, though none of t hese differences remained significant after correction for multiple compari sons. No association was found for any HLA class I allele. Haplotype analys is revealed a CLL-specific linkage disequilibrium for HLA-DRB1*0401:DRB4*01 03 and HLA-DRB4"0103:DQB1*0302. Our results suggest that CLL could be assoc iated with distinct class II alleles of the Caucasian haplotype HLA-DR4:DR5 3:DQ8, which has also been related to a susceptibility for several auto-imm une diseases. The positive, though weak, association of CLL with HLA-DPB1*0 301 might represent an independent susceptibility factor since no linkage d isequilibrium existed with any of the other CLL-associated alleles. None of the previously reported associations with HLA class I antigens was confirm ed. Our results suggest that factors within or close to the human MHC class II region confer susceptibility to CLL. <(c)> 2001 Wiley-Liss, Inc.