MICA,MICB Polymorphisms and Linkage Disequilibrium with HLA‐B in a Chinese Mongolian Population

Abstract

In this study, polymorphisms of major histocompatibility complex class I chain-related genes A and B (MICA and MICB) and human leucocyte antigen (HLA)-B gene were investigated for 158 unrelated Chinese Mongolian subjects recruited from central Inner Mongolia Autonomous Region, northern China, by polymerase chain reaction-sequence-based typing (PCR-SBT) and cloning. Collectively, 79 alleles, including 20 MICA, 12 MICB and 47 HLA-B alleles, were identified. MICA*008:01 (21.2%), MICB*005:02 (48.1%) and HLA-B*51:01 (7.91%) were the most common alleles. Significant global linkage disequilibrium (LD) was detected between HLA-B and MICA, HLA-B and MICB, and MICA and MICB loci (all P < 0.000001). The most frequent haplotypes were HLA-B*51:01-MICA*009:01 (7.28%), HLA-B*58:01-MICB*008 (6.96%), MICA*010-MICB*005:02 (13.92%) and HLA-B*58:01-MICA*002:01-MICB*008 (6.96%). HLA-B-MICA haplotypes such as HLA-B*50:01-MICA*009:02 were associated with single MICB allele. Some HLA-B-MICA haplotypes were associated with multiple MICB alleles, including HLA-B*51:01-MICA*009:01. One novel MICB allele, MICB*031, was identified, which has possibly arisen from MICB*002:01 through single mutation event. We also confirmed the existence of a recently recognized MICA allele, MICA*073, whose ethnic origin has not been previously described. Genotype distributions at MICA, MICB and HLA-B were consistent with a neutrality model. Our results provide new insight into MIC genetic polymorphisms in Chinese ethnic groups. Findings shown here are important from an anthropologic perspective and will inform future studies of the potential role of MIC genes in allogeneic organ transplantation and HLAlinked disease association in populations of related ancestry.

MICAGene Deletion in 3411 DNA Samples from Five Distinct Populations in Mainland China and Lack of Association with Nasopharyngeal Carcinoma (NPC) in a Southern Chinese Han population

“…The second and the third groups composed of 104 Han individuals and 158 Mongols, respectively, were recruited from the Inner Mongolia Autonomous Region, northern China (abbreviated as IMH and IMM in this study, respectively). The MICA*Del distribution has been reported for these two sample panels (Liu et al., ; Wang et al., ) using a typing strategy that required prior information of MICA‐STR (Tian et al., ). The MICA*Del frequencies were used for inter‐population comparison in this study.…”

“…An approximately 100‐kb genomic deletion spanning the entire MICA gene ( MICA*Del ) was initially identified on haplotypes bearing HLA‐B*4801 in a Japanese population (Komatsu‐Wakui et al ., ), later on HLA‐B*46 and HLA‐B*15 haplotypes in other ethnic groups (Komatsu‐Wakui et al., ; Aida et al., ). In most cases, MICA*Del is linked to MICB*009N , and to a less extent to MICB*005:02 (Komatsu‐Wakui et al., ; Komatsu‐Wakui et al., ; Aida et al., ; Liu et al., ; Wang et al., ).…”

A new MICA allele, MICA*007:07, characterized by cloning and sequencing

“…The HLA genotype was as follows: HLA‐A*02:06 , A*24:02 ; HLA‐B*27:05 , B*44:02 ; MICA*007:07 , MICA*008:01 ; MICB*004:01, MICB*005:02; HLA‐DRB1*03:01 , DRB1*15:01 . Previous studies have demonstrated consistent linkage between MICA*007 and HLA‐B*27:05, and between MICA*008:01 and HLA‐B*44:02 (Fodil et al., ; Wang et al., ), suggesting that MICA*007:07 was linked to HLA‐B*27:05 . MICA*007:07 was associated with MICA*A4 allele in exon 5.…”

“…Recently, we reported MICA and MICB allelic distributions in 158 individuals of Mongol ethnicity recruited from the Inner Mongolia Autonomous Region, northern China (Wang et al., ). To investigate further the extent of MICA polymorphism in the Mongolian ethnic group, collecting of new DNA samples has been initiated.…”

“…MICB genotyping was carried out by PCR‐SBT on exons 2, 3 and 4 of MICB gene as previously described (Liu, Tian, Li & Cai, ). HLA‐A , HLA‐B and HLA‐DRB1 were typed by PCR‐SBT using SeCore ® Locus A, B, DRB1 Single Amplification System (Life Technologies Shanghai, China) (Wang et al., ).…”