HLA Alleles, Genotype and Haplotype Analyzes from Central Anatolia Region of Turkey

Background: Although human leukocyte antigen (HLA) data for the Turkish population has been reported, there are no statistics on the HLA-DPB1 locus, which has recently received significant attention, particularly in hematopoietic stem cell transplantation. In addition, there is no study that has reported the 2-6 loci HLA haplotype distribution, 8-digit HLA allele frequency, and genotype frequency in the Turkish population. Aims: To evaluate the low and high resolution (2-4-8 digits) HLA-A, -B, -C, -DRB1, -DQB1, -DPB1 allele data using the data of 6100 healthy individuals from the Central Anatolian region of Turkey. Study Design: Retrospective cross-sectional study. Methods: All tests were performed using molecular HLA techniques: low-resolution DNA-based sequence-specific oligonucleotides, low/high-resolution DNA-based sequence-specific primer, and high-resolution next generation sequencing. A total of 6100 healthy donors with a minimum of 3 loci (HLA-A, -B, -DRB1) were analyzed for their HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 data. Pypop and HLA-net GENE[RATE] were used to analyze the data. Results: Among the HLA class I alleles, the following were the most frequently observed alleles: for HLA-A, A*02, A*24, A*03, and A*01; for HLA-B, B*35, B*51, and B*44; and for HLA-C, C*07, C*04, and C*12. Among the HLA class II alleles, the following alelles were the most frequently observed: for HLA-DRB1, DRB1*11, DRB1*04, and DRB1*13; for HLA-DQB1, DQB1*03, DQB1*05, and DQB1*06; and for HLA- DPB1, DPB1*04, DPB1*02, and DPB1*03. The most common alleles among HLA-DPB1 in the 4-digit evaluation were DPB1*04:01, DPB1*02:01, and DPB1*04:02. Among the HLA classes I and II, the following were the most frequently observed 8-digit alleles in HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 were A*02:01:01:01, B*49:01:01:01, C*04:01:01:06, DRB1*07:01:01:01, DQB1*03:01:01:02, and DPB1*02:01:02:05, respectively. The most common 6 loci haplotype was A*02~B*35~C*04~DRB1*11~DQB1*03~DPB1*04 (2.71%). Conclusion: In this study, low and high resolution HLA-DPB1 allele frequency, 6 locus haplotype frequency and genotype frequency were reported for the first time in Turkish population. These new data can be used to map HLA in our country and may provide ideas for potential future studies.

A Novel Finding of an HLA Allele's and a Haplotype's Relationship with SARS-CoV-2 Vaccine-Associated Subacute Thyroiditis.

Subacute thyroiditis (SAT) is a thyroid disease associated with viral infections. Its relationship with major histocompatibility complex (MHC) antigens was shown before. SAT cases triggered by different types of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been reported. In this study, human leukocyte antigen (HLA) genotypes of 27 SAT patients (13 vaccine-associated (V-SAT) and 14 non-SARS-CoV-2-infection non-vaccine-associated (non-V-SAT)) were compared with those of 362 healthy donors. HLA analyses were performed with low-resolution DNA-based sequence-specific oligonucleotide or sequence-specific primer methods. Statistical analyses were performed using IBM SPSS Statistics 25 and Stata/MP 14.1 with the hapipf function. Allele and haplotype frequencies were estimated by PyPop and gene[RATE] tool programs. The allele frequencies of HLA-A*11, HLA-B*35, and HLA-C*04 were higher in the patient groups. Both the allele frequency of HLA-A*11 and the haplotype frequency of A*11-B*35-C*04 were higher in the V-SAT group. The A*11-B*35-C*04 haplotype, including all three loci of MHC class I genes, is shown to be associated with the disease for the first time, especially in the V-SAT group. This finding will contribute to a better understanding of the etiopathogenesis of vaccine-associated SAT and the role of HLA genotypes in the functioning mechanisms of the SARS-CoV-2 vaccines.

Relationship Between Angiotensin II Type 1 Receptor Antibody Positivity and Cytokine Gene Polymorphism in Renal Transplant Patients When Organ Rejection Occurs.

OBJECTIVES: Kidney transplant remains the gold standard for the treatment of end-stage renal disease. Relationships between the presence of non-HLA antibodies, antibodies to AT1R, and cytokine gene polymorphisms with rejection have recently been shown. We sought to determine whether the presence of antibodies to AT1R and cytokine gene polymorphisms affected the development of rejection in pediatric and adult patients, whether a relationship is present between cytokine polymorphism and level of antibodies to AT1R, and whether their presence can be a biomarker pretransplant. MATERIALS AND METHODS: Our study included 100 pediatric and adult kidney transplant patients plus 50 healthy controls. Levels of AT1R antibodies (by enzyme-linked immunosorbent assay) and gene polymorphisms of the cytokines transforming growth factor ß, tumor necrosis factor α, interleukins 6 and 10, and interferon gamma cytokines (by sequence- specific primer-polymerase chain reaction) were studied retrospectively and evaluated with the SPSS statistical program. RESULTS: We found no statistically significant relationship between levels of antibodies to AT1R and gene polymorphisms among the studied cytokines in patients with rejection compared with the healthy controls and patients with uneventful courses posttransplant. However, higher levels of antibodies to AT1R were observed in pediatric compared with adult transplant recipients (P < .001). A statistically significant relationship was also observed between transforming growth factor ß1 C/C G/C low-release and interleukin 6 G/C high-release gene polymorphism and levels of antibodies to AT1R (P < .001). CONCLUSIONS: Because we observed that some gene polymorphisms among the studied cytokines may affect AT1R antibody levels, future studies are needed to understand the mechanism of the relationship. In addition, studies with larger groups are required to sufficiently confirm that higher antibody levels are present in pediatric versus adult patients.