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 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, p < 0.0025] 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.
Machulla
H K
HK
Interbranch HLA Laboratory, Institute of Medical Immunology, Martin-Luther-University of Halle, Magdeburger Str. 16, D-06097 Halle, Germany. helmut.machulla@medizin.uni-halle.de
Müller
L P
LP
Schaaf
A
A
Kujat
G
G
Schönermarck
U
U
Langner
J
J
D000483:Alleles; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D005858:Germany; D006682:HLA-DP Antigens / Q000235:genetics; D059868:HLA-DP beta-Chains; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D015804:HLA-DR4 Antigen / Q000235:genetics*; D059845:HLA-DRB4 Chains; D006239:Haplotypes; D006650:Histocompatibility Testing; D006720:Homozygote; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008297:Male; D008875:Middle Aged
D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D006683:HLA-DQ Antigens; C109756:HLA-DQ8 antigen; D006684:HLA-DR Antigens; D015804:HLA-DR4 Antigen; C050610:HLA-DR53; D059845:HLA-DRB4 Chains