MICB Polymorphism In Northern And Southern Chinese Han Populations And HLA-E Polymorphism In Four Distinct Populations In Mainland China

Objective Human leukocyte antigen (HLA) gene complex maps to6p21.3encompassing a segment of approximately4Mb. In contrast to the classical HLA genes,which have been intensively investigated for their extraordinary polymorphisms, the data are still limited about the genetic variations of non-classical HLA genes in Chinese populations residing in different geographic locations or with different ethnic background. In the first part of our study,104healthy, unrelated Han subjects recruited from central Inner Mongolia Autonomous Region, northern China, were investigated for MICB allelic variation, the association of MICB alleles with AluyMICB insertion/deletion dimorphism located in MICB intron1, linkage disequilibrium of MICB with HLA-B and MICA, and HLA-A-C-B-MICA-MICB haplotypic diversity. We then investigated the MHC class I chain-related gene B (MICB) allelic variation in201healthy, unrelated Han subjects from Hunan province, southern China. In the second part of our study, we investigated HLA-E allelic polymorphism and the characteristics of LD between HLA-A and HLA-E loci in four Chinese populations, with an emphasis on HLA-A-E-C-B haplotypic diversity in a southern (Hunan Province) and a northern (Inner Mongolia Autonomous Region) Chinese Han population.Methods We investigated the MICB allelic variation by sequence-based typing (SBT) in the northern and southern Chinese Han populations. HLA-E allelic typing was performed for690individuals from two southern Chinese Han populations (Hunan Han and Guangdong Han) and two northern Chinese populations (Inner Mongolia Han and Inner Mongolia Mongol) using polymerase chain reaction-sequence-specific priming (PCR-SSP) method.Result In the northern Chinese Han population, ten kinds of MICB alleles were observed, among which MICB*005:02/010, MICB*002:01, and MICB*004:01were the most frequent alleles with frequencies of51.44%,16.35%,11.54%, respectively. Significant LD was observed for9of the21HLA-B-MICB haplotypes and6of the17MICA-MICB haplotypes with a frequency>1.5%. In particular, HLA-B*13:01and HLA-B*13:02, both of which were frequently represented in this population, showed distinct LD pattern with MICB allele. A new MICB allele, MICB*023, was identified, which differed from MICB*005:02/010by a single mutation of G to A at position86in exon2, resulting in an amino acid change from arginine to histidine at codon6.HLA-A*30-C*06-B*13:02-MICA*008:01-MICB*005:02/010was the most common haplotype with a frequency of8.64%in this population. HLA-A*02-C*08-B*48-MICA*Del-MICB*009N showed a frequency of2.4%in this population.In the southern Chinese Han population, eleven MICB alleles were observed, among which MICB*005:02predominated with a frequency of64.93%. Significant linkage disequilibrium (LD) was observed for5HLA-B-MICB and6MICA-MICB haplotypes. Compared with a northern Chinese Han population, several MICB haplotypes appeared to be highly specific to this southern Chinese Han population. Two new MICB alleles, MICB*005:06and MICB*026, were identified. Aligned with MICB*005:02, MICB*005:06has a synonymous T replacement at nucleotide762in exon4; MICB*026has probably arisen from MICB*004:01through a single nucleotide substitution from G to A at position826in exon4, leading to an amino acid change from glutamic acid to lysine at codon253. HLA-A*02-C*01-B*46-MICA*010-MICB*005:02-DRB1*09was the most prevalent six-locus haplotype with a frequency of8.49%. HLA-A*30-C*06-B*13:02-MICA*008:01-MICB*005:02-DRB1*07appeared to be a conserved extended haplotype.HLA-E study data showed that (1) HLA-E*01:01and HLA-E*01:03, but not E*01:04allele, were detected in the four populations, HLA-E distribution differed significantly between each of the two southern Chinese Han populations and the Inner Mongolia Mongol population, and between Hunan Han population and Inner Mongolia Han population;(2) HLA-G*01:05N-A*30-E*01:01-C*06-B*13:02-DRB1*07was a conserved extended haplotype in the Chinese Han populations;(3) five HLA-A-E haplotypes showed significant linkage disequilibrium (LD) in at least one population, including HLA-A*02-E*01:03in populations except for the Inner Mongolia Mongol group, HLA-A*01-E*01:01and HLA-A*30-E*01:01in the Hunan Han and the Inner Mongolia Han populations, HLA-A*33-E*01:01in the two southern Chinese Han populations and HLA-A*03-E*01:03in the Inner Mongolia Mongol group; and (4) Ewens-Watterson homozygosity test showed a trend for balancing selection at the HLA-E locus in each of the four populations. Our data unraveled the peculiarity in terms of HLA-E allelic and haplotypic repertoire in four main ethnic groups in Mainland China, findings shown here are valuable for future studies of the potential role of HLA-E in allogeneic organ transplantation and HLA-linked disease association in related ethnic groups.Conclusion Our result provided for the first time the data about MICB genetic polymorphism in Chinese Han populations, and unravelled the peculiarity in terms of HLA-E allelic and haplotypic repertoire in four main ethnic groups in mainland China, findings shown here are valuable for future studies of the potential role of MICB and HLA-E in allogeneic organ transplantation and HLA linked disease association in related ethnic groups, and provides preliminary data for future haplotype maping.