Analysis of HLA frequencies in donor population of Unrelated Bone Marrow Donor and Cord Blood Registry of Institute of Haematology and Blood Transfusion

Jacek Nowak, Anna Gronkowska, Ewa Brojer

The HLA alleles and haplotypes frequencies of Polish population are helpful in the routine work of HLA laboratory and in searching of unrelated bone marrow donors for Polish patients. HLA I class typing was performed by standard serological method in 2580 potential donors from Poland, and HLA DRB1 DNA typing by PCR-SSP or PCR-SSOP at low resolution level in 386 donors chosen by chance from the said population. Allelic and haplotypic (2 or 3 loci haplotype) gene frequencies were estimated by iterative maximum likelihood gene counting method supplemented by expectation maximization and Hardy-Weinberg equilibrium algorithm using ML-EM-HW v. 5.2 software elaborated in our Institute. The resolution of used methods was: 24 specificities of HLA-A, 46 HLA-B, 11 HLA-Cw, and 17 HLA*DRB1. There was a different portion of HLA “blank” in each locus. Allele gene frequencies were comparable with other Central Europe population frequencies. Estimated and observed antigen phenotypic frequencies were very similar. Fit to Hardy-Weinberg equilibrium was tested by c2 test for each locus separately and was good (p=1.0000). The highest positive linkage was found in following two-locus haplotypes: A*01-B*08 (GF 0.0739, D 0.0613, p<0.0001), A*03-B*07 (GF 0.0504, D 0.0333, p<0.0001) and A*25-B*18 (GF 0.0334, D 0.0288, p<0.0001). Very high, but negative linkage was found for A*02-B*08 (GF 0.0075, D -0.0215, p<0.0001) and A*01-B*18 (GF 0.0010, D -0.0095, p<0.0001) two-locus haplotypes. Sixteen HLA-A-B-DRB1 three-locus haplotypes showed gene frequency above 1%. Alleles of each of these haplotypes are in strong positive gametic linkage. The most frequent haplotypes in Polish population are: A*01-B*08-DRB1*03 (7.5%) and A*03-B*07-DRB1*15 (3.4%). It was tested by Chi2 test that Czech, Russian, German and Finn populations are most similar to Polish comparing three most frequent HLA-A,B,DRB1 haplotypes in these populations.

HLA-C allele distribution in Poles: comparison with other human populations
Laboratory of Immunogenetics, Department of Clinical Immunology, Ludwik Hirszfeld


Institute, Polish Academy

In contrast to HLA-A and HLA-B, physiological importance of HLA-C was long neglected
due to poor resolution of its polymorphism by serology. However, introduction of molecular
biology techniques resulted in realization that HLA-C has only two times lower number of
alleles (128) than HLA-A (266). There is growing interest in HLA-C because of its recently
described role in unrelated bone marrow transplant rejection and in resistance to natural killer
cells. Therefore, a knowledge of HLA-C allele distribution in a given human population is
highly desirable, and has already been performed for several Caucasians and non-Caucasians
populations. We describe here results of HLA-C typing of Polish population from Lower
Silesia region. 207 unrelated healthy persons were typed for HLA-C alleles by low resolution
PCR-SSP (Dynal, Olerup, Biotest). Similarly to other Caucasoid populations, HLA-Cw*07
was most frequent (0.3067), followed by HLA-Cw*12 (0.1400), HLA-Cw*04 (0.1376) and
HLA-Cw*03 (0.0918), whereas least frequent alleles (frequencies < 0.02) were HLA-Cw*14
and HLA-Cw*15, and HLA-Cw*18 was absent. Comparison with HLA-C frequency data
published for other ethnic groups revealed highest similarities to Germans, Slovaks and
Englishmen, lesser similarity to other Europeans, and, as expected, much lower degree of
similarity to non-Caucasoid populations.