Major histocompatibility complex class I chain‐related gene A polymorphism and linkage disequilibrium with HLA‐B alleles in Euro‐Brazilians

Abstract

Major histocompatibility complex class I chain-related gene A (MICA) was identified within the human leukocyte antigen (HLA) class I region and was located 46 kb centromeric from HLA-B locus. It functions as a ligand for human gammadelta T, CD8 T and natural killer (NK) cells by binding the NKG2D receptor. The aims of the present study were to determine the distribution of MICA alleles and MICA-HLA-B haplotypes in a sample of Euro-Brazilians. Through the combination of three typing methods, polymerase chain reaction (PCR)-sequence-specific oligonucleotide probe, PCR-sequence-specific primer and PCR-restriction fragment length polymorphism, 19 alleles were detected besides a MICA gene deletion in a sample composed by 204 unrelated Euro-Brazilians. The most commonly observed alleles were: MICA*00801 (25.3%), MICA*00201 (17.7%) and MICA*00901 (13.7%). The GCT repeat polymorphism variant A6 was the most commonly found. The most frequent haplotype found in this study was MICA*00901-B*51 (8.1%), followed by haplotypes MICA*00201-B*35 (6.1%) and MICA*00801-B*07 (6.1%). MICA*00801 truncated product, and its low affinity for NKG2D receptor may work as an inhibitor in its putative soluble form. It may also be that selective forces may favor MICA*00801 heterozygosity with NKG2D high affinity MICA alleles enabling activation and inhibition of cytotoxic activity of cells expressing the NKG2D receptor. The possibility of selective neutrality or of balancing selection still provides no explanation for MICA gene polymorphisms. Is it maintained by genetic drift or by the influence of migratory waves? Are there favored alleles while others present the same adaptive value?

Evaluation of the Humoral Immune Response to Human Leukocyte Antigens in Brazilian Renal Transplant Candidates

“…Southern Brazil was settled mainly by Europeans, but also has significant numbers of people of African descent and Native Americans in the population [39]. This influence can be observed in the results of this study, which revealed a predominant contribution of HLA allele groups of European origin, such as HLA-A*24 and -B*44 [41]–[43], as well as the occurrence of allele groups of African influence such as HLA-A*30 and -B*15 [44], [45].…”

HLA-A, -B, and -DRB1 allelic and haplotypic diversity in a sample of bone marrow volunteer donors from Rio Grande do Sul State, Brazil

“…In locus B the most common allelic groups were HLA-B*35, -B*44, -B*51, and -B*15, and in locus DRB1 the HLA-DRB1*13, -DRB1*07, -DRB1*04, and -DRB1*11 alleles were the most common. The data indicate a more representative contribution of alleles of European origin [27][28][29]. By contrast, the data also indicate the occurrence of alleles of African influence, such as HLA-B*15.…”

Predisposition to idiopathic thrombocytopenic purpura maps close to the major histocompatibility complex class I chain-related gene A

“…However, MICA maps close to the HLA-B locus, which demonstrated an allele association with ITP in previous studies [8,10]. Indeed, MICA and HLA-B loci were in linkage disequilibrium in several populations studies [23][24][25][26][27]. Moreover, some authors detected a strong association between the STR-MICA A5.1 allele (STR-MICA*183 allele in our study), which is associated with the MICA*008 extracellular allele [23], and the HLA-B*08 allele [15,28,29].…”