Grubic Zorana, Maskalan Marija, Svilicic Danijela, Stingl Jankovic Katarina, Zunec Renata
Clinical Hospital Center Zagreb, Tissue Typing Center, Zagreb, Croatia.
Arch Immunol Ther Exp (Warsz). 2016 Dec;64(Suppl 1):83-88. doi: 10.1007/s00005-016-0445-3. Epub 2017 Jan 12.
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 A02:01 (30.39%), A11:01 (13.37%), A24:02 (10.91%); B51:01 (12.48%), B18:01 (8.35%), B08:01 (8.06%); DRB103:01 (11.20%), DRB101:01 (9.84%), DRB116:01 (9.63%). The following HLA alleles were detected only once: A02:09, A24:03, A24:04, A24:07; B07:04, B15:07, B15:08, B39:04, B39:10, B39:24, B40:04; DRB108:03, DRB111:06, DRB113:32, DRB114:05. Five most frequent haplotypes were: A01:01-B08:01-DRB103:01 (5.34%), A02:01-B18:01-DRB111:04 (1.57%), A02:01-B27:02-DRB116:01 (1.50%), A02:01-B27:05-DRB101:01 (1.42%) and A02:01-B44:02:01G-DRB116:01 (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-A26:01-B38:01-DRB104:02 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.
在本研究中，对克罗地亚家庭中的HLA等位基因和单倍型频率进行了调查，以评估有关HLA基因型的有价值信息，并将其与克罗地亚骨髓捐献者登记处（CBMDR）的数据进行比较。总共纳入了350个为造血干细胞移植目的而进行分型的家庭。所有个体均使用PCR-SSO或PCR-SSP方法检测HLA-A、-B和-DRB1等位基因。通过分离确定HLA-A-B-DRB1单倍型并直接计数。共鉴定出30个HLA-A、54个HLA-B和38个HLA-DRB1等位基因以及716种不同的HLA-A-B-DRB1单倍型。其中，HLA-A、-B和-DRB1位点最常见的三个等位基因分别为A02:01（30.39%）、A11:01（13.37%）、A24:02（10.91%）；B51:01（12.48%）、B18:（8.35%）、B08:01（8.06%）；DRB103:01（11.20%）、DRB101:01（9.84%）、DRB116:01（9.63%）。以下HLA等位基因仅被检测到一次：A02:09、A24:03、A24:04、A24:07；B07:04、B15:07、B15:08、B39:04、B39:10、B39:24、B40:04；DRB108:03、DRB111:06、DRB113:32、DRB114:05。五种最常见的单倍型为：A01:01-B08:01-DRB103:01（5.34%）、A02:01-B18:01-DRB111:04（1.57%）、A02:01-B27:02-DRB116:01（1.50%）、A02:01-B27:05-DRB101:01（1.42%）和A02:01-B44:02:01G-DRB116:01（1.28%）。将基于家庭研究的单倍型频率与CBMDR的频率进行比较，除了HLA-A26:01-B38:01-DRB104:02单倍型外，其他结果相似。在家庭个体中观察到该单倍型的频率显著更高（P = 0.0017）。有九种单倍型是独特的，目前的数据库中不存在它们的频率数据。本研究获得的数据可能对人类学、移植和疾病关联研究有用。
