A study of the frequencies of HLA-DQA1 alleles and their clinical application values in the donor-recipient HLA-10/10 matched hematopoietic stem cell transplantation

Abstract

Objective To analyze the frequencies of HLA-DQA1 alleles and their clinical values in the donor-recipient HLA-A, -B, -C, -DRB1, -DQB1(10/10) matched hematopoietic stem cell transplantation(HSCT). Methods This study recruited 127 patients who received allogeneic HSCT and 127 unrelated donors. High-resolution (High Res) DNA typing for HLA-DQA1 alleles were performed on the 254 subjects by using sequence specific oligonucleotide probes(SSOP) and high resolution of sequence specific primer(High Res SSP). Results The DQA1 allele genotypes of 36 pairs of donor-recipient were directly identified by using SSOP. The ambiguous DQA1 allele genotypes of the rest 91 pairs were identified by using High Res SSP. Among the 127 pairs of donor-recipient, 5 pairs were HLA-DQA1 alleles mismatched, while the others were all matched. No significant differences in the distribution of HLA-DQA1 alleles were observed between the donors and the recipients. Sixteen HLA-DQA1 alleles were detected in the 127 donors, which were DQA1*02∶01 (19.3%), DQA1*01∶02(19.3%), DQA1*03∶02/03(17.0%), DQA1*01∶03 (9.8%), DQA1*06∶01(9.1%), DQA1*05∶01(7.1%), DQA1*05∶05(5.9%), DQA1*03∶01 (4.7%), DQA1*01∶04(2.4%), DQA1*01∶05(2.0%), DQA1*01∶01(1.2%), DQA1*05∶03(0.8%), DQA1*05∶08(0.8%), DQA1*04∶01(0.4%), DQA1*05∶06(0.4%) from high to low frequency. Moreover, a new allele was detected in the patients. The haplotypes' frequencies and linkage disequilibrium(LD) analysis of HLA-DQA1 and HLA-DQB1 showed that the most common haplotype was DQA1*02∶01-DQB1*02∶02(16.1%), followed by DQA1*03∶02/03-DQB1 *03∶03 (11.8%) and DQA1*01∶03-DQB1*06∶01 (9.1%). Stronger LD were observed between DQA1*02∶01 and DQB1*02∶02, DQA1*03∶02 and DQB1*03∶03, DQA1*01∶03 and DQB1*06∶01, HLA-DQA1*06∶01 and DQB1*03∶01, DQA1*05∶01 and DQB1*02∶02(P<0.001). Conclusion There was strong linkage disequilibrium between HLA-DQA1 and HLA-DQB1 genes. The polymorphism of HLA-DQA1 gene was less than that of HLA-DQB1 gene. No more guidance was provided to donor selection in unrelated donor-recipient HLA matched HSCT by adding HLA-DQA1 genotyping, but it might have clinical application values in HSCT with HLAⅡ locus mismatched donor and recipient. Key words: High resolution; HLA-DQA1 gene; HLA-DQB1 gene; Gene frequency; Linkage disequilibrium