Determination of HLA-A, -B, and -DRB1 Allele and Haplotype Frequencies in the Croatian Population Based on a Family Study.

In the present study, HLA allele and haplotype frequencies among Croatian families were investigated to evaluate valuable information about HLA genotypes and to compare them with data from the Croatian Bone Marrow Donor Registry (CBMDR). A total of 350 families which have been typed for the purpose of HSCT were included. All individuals were tested using PCR-SSO or PCR-SSP methods for HLA-A, -B, and -DRB1 alleles. The HLA-A-B-DRB1 haplotypes were determined by segregation and directly counted. A total of 30 HLA-A, 54 HLA-B, and 38 HLA-DRB1 alleles and 716 different HLA-A-B-DRB1 haplotypes were identified. Of these, the three most frequent alleles at HLA-A, -B, and -DRB1 loci, respectively, were A*02:01 (30.39%), A*11:01 (13.37%), A*24:02 (10.91%); B*51:01 (12.48%), B*18:01 (8.35%), B*08:01 (8.06%); DRB1*03:01 (11.20%), DRB1*01:01 (9.84%), DRB1*16:01 (9.63%). The following HLA alleles were detected only once: A*02:09, A*24:03, A*24:04, A*24:07; B*07:04, B*15:07, B*15:08, B*39:04, B*39:10, B*39:24, B*40:04; DRB1*08:03, DRB1*11:06, DRB1*13:32, DRB1*14:05. Five most frequent haplotypes were: A*01:01-B*08:01-DRB1*03:01 (5.34%), A*02:01-B*18:01-DRB1*11:04 (1.57%), A*02:01-B*27:02-DRB1*16:01 (1.50%), A*02:01-B*27:05-DRB1*01:01 (1.42%) and A*02:01-B*44:02:01G-DRB1*16:01 (1.28%). The haplotype frequencies based on the family study were compared with the frequencies from CBMDR, and similar results were obtained for all except for the HLA-A*26:01-B*38:01-DRB1*04:02 haplotype. A significantly higher frequency (P = 0.0017) of this haplotype was observed among family individuals. Nine haplotypes were unique and data about their frequencies do not exist in current databases. The data obtained in this study could be useful for anthropology, transplantation and disease association studies.

[Haplotipic associations of the two most common HLA-B*27 alleles in the Croatian population]. / Haplotipske veze dva najcesca podtipa gena HLA-B*27 u hrvatskoj populaciji.

The aim of the present study was to analyze haplotypic associations of two the most common HLA-B*27 subtypes (B*2702 and *2705) in the Croatian population. One hundred and eleven unrelated HLA-B*27 positive individuals were included. None of them had any sign of ankylosing spondylitis. The total number of analyzed haplotypic associations was 112 because one individual was homozygous for HLA-B*27. HLA-B*27 alleles as well as HLA-A and DRB1 specificities were tested by PCR-SSP method. Among seven different HLA-B*27 alleles observed among our individuals, B*2705 was the most frequent (61.6%), followed by B*2702 (30.4%), while the frequency of all other observed alleles (B*2701, B*2703, B*2704, B*2708 and B*2714) was less than 2.0%. HLA-A*02 was the most frequent specificity at HLA-A locus in both groups of haplotypic associations (B*2702 and B*2705) and no difference in distribution of HLA-A genes was observed between two groups. Analysis of HLA-B*2702 haplotypic associations showed the high frequency of DRB1*16 (44.2%) in comparison to B*2705 haplotypic associations (4.0%) with significant P value (P<0.00001). HLA-DRB1*01 demonstrated significantly higher presence among 69 B*2705 haplotypic associations compared to 34 B*2702 haplotypic associations (28.0% vs. 1.5%; P<0.00001).