No abstract

HLA-E is a non-classical I (Ib) gene which has limited polymorphism and low levels of tissue expression. Currently, 11 alleles are described in the literature with only three protein products. In the present study we investigated HLA-E gene variations at exons 2 and 3 and calculated allele, genotype and haplotype frequencies in a sample of 152 individuals who reported themselves as being Afro-descendants and who are voluntary bone marrow donors living in the state of Paraná, Brazil. The most frequent allele in the sample analyzed was the E(∗)01:01 (59.21%). The presence of the E(∗)01:04 allele was not detected suggesting that it has a very low worldwide frequency or that this allele may be an artifact of sequencing. We reported the most frequent alleles found as well as genotypes and haplotypes and compared our results with the few other studies found in the literature. This study is the first to investigate Afro-descendants from the South of Brazil.

The results suggest that the distribution of HLA-G products may play a significant role in the modulation of maternal-fetal immune response.

These results suggest that HLA-E allelic variants may play a role in the modulation of immune responses in the context of the inability of natural conception and establishment of a viable pregnancy.

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The human leukocyte antigen (HLA) are the most polymorphic genes in the human genome. Because of their importance for antigen recognition, HLA molecules play a central role in host defense and graft rejection upon transplantation. The aim of this study was to characterize allelic diversity of the classical HLA genes HLA‐A, ‐B, ‐C, ‐DRA, ‐DRB1, ‐DQA1, ‐DQB1, ‐DPA1, ‐DPB1, and the non‐classical class I genes HLA‐E, ‐F and ‐G at high‐resolution for a population of predominantly European ancestry from Curitiba, Brazil. Genotyping of 108 individuals was performed by next‐generation sequencing on the MiSeq platform and also by Sanger sequencing. The genotype distributions of all loci were in accordance with Hardy‐Weinberg equilibrium (P > 0.05) and a total of 202 HLA variants at second field resolution were observed for the 12 loci. The strongest linkage disequilibrium (r2 = 1.0, P < 10−5) was observed for the following pairs of alleles: HLA‐B*42:01:01 ~ HLA‐DRB1*03:02:01; HLA‐B*14:02:01 ~ HLA‐C*08:02:01; B*42:01:01 ~ HLA‐C*17:01:01; HLA‐DRB1*03:01:01 ~ HLA‐DQB1*02:01:01 ~ DRB1*03:01:01 ~ HLA‐DQB1*02:01:01; DRB1*13:01:01~ HLA‐DQB1*06:03:01 and HLA‐DRB1*09:01:02 ~ HLA‐DQA1*03:02. This is the first study to characterize all 12 HLA genes at high resolution in a single population. On the basis of the allelic frequencies of worldwide populations and principal component analysis, we confirmed the similarity of the study population to European and other Euro‐descendant populations.

The major histocompatibility complex (MHC) class I chain-related gene A (MICA) is located centromerically to the human leukocyte antigen (HLA)-B. The short distance between these loci in the MHC indicates the presence of linkage disequilibrium (LD). Similarly to the HLA, the MICA is highly polymorphic, and this polymorphism has not been well documented in different populations. In this study, we estimated the allelic frequencies of MICA and the linkage disequilibrium with HLA-B alleles in 346 renal-transplant candidates in southern Brazil. MICA and HLA were typed using the polymerase chain reaction-sequence-specific primer method (PCR-SSO), combined with the Luminex technology. A total of 19 MICA allele groups were identified. The most frequent allele groups were MICA*008 (21.6%), MICA*002 (17.0%) and MICA*004 (14.8%). The most common haplotypes were MICA*009-B*51 (7.8%), MICA*004-B*44 (6.06%) and MICA*002-B*35 (5.63%). As expected from the proximity of the MICA and HLA-B loci, most haplotypes showed strong LD. Renal patients and healthy subjects in the same region of Brazil showed statistically significant differences in their MICA polymorphisms. The MICA*027 allele group was more frequent in renal patients (Pc = 0.018, OR: 3.421, 95% CI: 1.516–7.722), while the MICA*019 allele group was more frequent in healthy subjects (Pc = 0.001, OR: 0.027, 95% CI: 0.002–0.469). This study provided information on the distribution of MICA polymorphisms and linkage disequilibrium with HLA-B alleles in Brazilian renal-transplant candidates. This information should help to determine the mechanisms of susceptibility to different diseases in patients with chronic kidney disease, and to elucidate the mechanisms involved in allograft rejection associated with MICA polymorphisms in a Brazilian population.

No abstract