The association between MICA/MICB polymorphism and respiratory syncytial virus infection in children

MICA/MICB gene polymorphisms are related to several cancers and infectious diseases, but there are no reports on the association between MICA/MICB gene polymorphisms and respiratory syncytial virus (RSV) infection. To clarify the association between MICA/MICB gene polymorphisms and infection of RSV in children, we collected fresh blood samples from paediatric patients with and without pneumonia after RSV infection. The MICA/MICB alleles were characterized by PCR sequence‐specific primers (PCR‐SSP) and PCR sequence‐based genotyping (PCR‐SBT), and then, the frequency of the MICA/MICB alleles and haplotypes was calculated. The results showed that the frequencies of MICA*002:01 and MICA‐A9 in RSV‐infected patients were significantly lower than in controls (9% vs. 20%, pc = 0.04). The allele frequency of MICA*002:01 in pneumonia patients (8%) and nonpneumonia patients (9%) was significantly lower than in controls (20%, pc = 0.02). MICA*002:01‐MICB*008(Δrel = 0.616), MICA*009‐MICB*016 (Δrel = 0.506), and MICA*045‐MICB*014 (Δrel = 0.700) showed linkage disequilibrium in patients infected with RSV. The haplotype frequency of MICA*002:01‐MICB*005:02 in RSV‐infected patients was significantly lower than in controls (10% vs. 16%, pc = 0.033). In conclusion, allele MICA*002:01/A9 and haplotype MICA*002:01‐MICB*005:02 were negatively associated with RSV respiratory tract infections.     

MICA Gene 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

Deletion of major histocompatibility complex class I chain‐related genes A (MICA*Del) was investigated in 3,411 DNA samples from two southern Chinese Han populations (Hunan Han, HNH; Guangdong Han, GDH), two northern Chinese populations (Inner Mongolia Han, IMH; Inner Mongolia Mongol, IMM) and one southeastern Chinese Han population (Fujian Han, FJH) using an in‐house polymerase chain reaction‐sequence specific priming (PCR‐SSP) assay, which enables direct discrimination between heterozygote and homozygote for MICA*Del. MICA*Del showed a frequency ranging from 0.8% in FJH to 5.7% in IMM (P_corrected < 0.05), indicating northward increase in frequency of MICA*Del in Chinese populations. In contrast to the association reported recently in a Taiwan Chinese population and a Malaysian Chinese cohort, MICA*Del distribution did not differ between 1,120 patients with nasopharyngeal carcinoma (NPC) and 1,483 normal controls in the HNH population (1.03% in NPC cases vs 1.18% in the controls, OR (95% CI) = 0.87 (0.51‐1.47), p = 0.69). Further gender‐stratified analysis also failed to disclose any male‐specific association reported in a Taiwan Chinese population. Multi‐locus typing of the 94 samples carrying MICA*Del revealed two new haplotypes, HLA‐A*11:01‐B*13:01‐MICA*Del‐MICB*009N‐DRB1*04:06 and HLA‐B*35:01‐MICA*Del‐MICB*009N‐DRB1*15:01, in addition to HLA‐B*48‐MICA*Del. Unexpectedly, two samples with MICA*Del in the HNH population were each consistently found to have two distinct MICA alleles, indicating the existence of two MICA gene copies on certain HLA haplotypes. Based on the results from a sizeable case‐control study, our data suggest that there is no association between MICA*Del and NPC in the southern Chinese Han population.     

Allele polymorphism and haplotype diversity of MICA/B in Tujia nationality of Zhangjiajie,Hunan Province,China

Previous studies indicate the distribution of major histocompatibility complex class I chain-related genes A (MICA) and B (MICB) alleles and haplotypes varies widely between different ethnic populations and geographic areas. It is meaningful to investigate allelic frequencies and establish a genetic database. In this study, we firstly reported the polymorphic variation of MICA/B in 187 healthy, unrelated Tujia individuals in Zhangjiajie region, China. Using polymerase chain reaction-sequence specific priming (PCR-SSP) and sequencing-based typing (PCR-SBT), we identified eight MICA-sequence alleles, four MICA-short tandem repeat variants, and 13 MICB variants, of which MICA¹008:04 (29.41%), MICA¹A5 (29.68%), MICA¹A5.1 (29.68%) and MICB¹005:02 (39.57%) were the most frequent. Linkage disequilibrium analysis further revealed MICB¹005:02-MICA¹019 (13.10%) and MICB¹002-MICA¹008:04 (9.89%) as the most common two-locus haplotypes. Data comparison by neighbor-joining dendrograms and principal component analysis to verify allelic frequencies in other Chinese and Asia ethnic groups showed that the Zhangjiajie Tujias were genetically closer to the Guangdong Han population, based on MICA loci variability. Our results provide new information about the MICA/B gene polymorphism in Chinese Tujia population, which will form the basis for future studies on the potential role of MICA/B in allogeneic organ transplantation and disease susceptibility in related ethnic groups.     

MICB polymorphisms and haplotypes with MICA and HLA alleles in Koreans

Major histocompatibility complex (MHC) class I chain-related gene B (MICB) is located within the human MHC class I region. The location of MICB in the MHC region may imply the presence of linkage disequilibrium with polymorphic MICA and human leukocyte antigen (HLA) loci. MICB is also polymorphic; however, MICB polymorphisms have not been investigated in Koreans. Using sequence-based typing (SBT), we estimated the allelic frequencies of MICB and haplotypes with MICA, HLA-B, and HLA-DRB1 at high resolution in a population of 139 unrelated Korean individuals. Eight MICB alleles were identified. The most frequent allele was MICB*005:02/*010 (57.2%), followed by *002 (11.5%), *004 (8.3%), *005:03 (8.3%), and *008 (6.8%). The most common two-locus haplotypes were MICB*005:02/*010-MICA*010 (19.4%), MICB*005:02/*010-DRB1*15:01 (6.5%), and MICB*005:02/*010-B*15:01 (10.4%); the most common three-locus haplotypes were B*15:01-MICA*010-MICB*005:02/*010 (5.8%) and MICA*010-MICB*005:02/*010-DRB1*04:06 (10.4%); and the most common four-locus haplotype was B*15:01-MICA*010-MICB*005:02/*010-DRB1*04:06 (5.8%). This is the first study to provide information about MICB allele frequencies and haplotypes with HLA in Koreans. These study results should help understand mechanisms of disease association between the MICB locus and neighboring loci in Koreans.     

MIC gene polymorphism and haplotype diversity in Zhuang nationality of Southern China

Zhuang ethnic minority is the largest minority group in China. Here, we report for the first time the polymorphisms of MICA and MICB in a healthy Zhuang population of 209 unrelated individuals. Using polymerase chain reaction-sequence specific priming (PCR-SSP) and sequencing-based typing (PCR-SBT), 13 MICA-sequence alleles and 5 MICA-STR alleles, as well as 11 MICB alleles were detected, among which MICA^∗010, MICA^∗A5 and MICB^∗005:02 were the most frequent alleles. Linkage disequilibria was investigated and the most common two-locus haplotypes were MICB^∗005:02-MICA^∗010 and MICB^∗014-MICA^∗045. These results suggest informative genetic markers for investigating origins and evolution of MHC class I region haplotypes in Zhuang population.     

Characterization of the major histocompatibility complex class I chain-related gene B (MICB) polymorphism in a northern Chinese Han population: the identification of a new MICB allele, MICB*023

Major histocompatibility complex class I chain-related gene B (MICB) has only been characterized for allelic variation in very few human populations. The MICB polymorphism remains largely unknown in Chinese populations. In this study, 104 healthy unrelated Han subjects recruited from central Inner Mongolia Autonomous Region, northern China, were investigated by sequence-based typing for MICB allelic variation, the association of MICB alleles with AluyMICB insertion/deletion dimorphism located in MICB intron 1, linkage disequilibrium of MICB with human leukocyte antigen (HLA)-B and MICA, and HLA-A-C-B-MICA-MICB haplotypic diversity. Ten kinds of MICB alleles were observed, among which MICB*005:02/010, MICB*002:01, and MICB*004:01 were the most frequent alleles with frequencies of 51.44, 16.35, and 11.54%, respectively. Significant linkage disequilibrium (LD) was observed for 9 of the 21 HLA-B-MICB haplotypes and 6 of the 17 MICA-MICB haplotypes with a frequency >1.5%. In particular, HLA-B*13:01 and HLA-B*13:02, both of which were frequently represented in this population, exhibited a distinct LD pattern with the MICB allele. A new MICB allele, MICB*023, was identified, which differed from MICB*005:02/010 by a single mutation of G to A at position 86 in exon 2, resulting in an amino acid change from arginine to histidine at codon 6. HLA-A*30-C*06-B*13:02-MICA*008:01-MICB*005:02/010 was the most common haplotype, with a frequency of 8.64% in this population. HLA-A*02-C*08-B*48-MICA*Del-MICB*009N demonstrated a frequency of 2.4% in this population. Our results provide for the first time data regarding the MICB genetic polymorphism in northern Chinese Han populations and will form the basis for future studies of the potential role of MICB in allogeneic organ transplantation and disease association in related ethnic groups.     

HLA‐A, ‐B and ‐DRB1 polymorphism in Koreans defined by sequence‐based typing of 4128 cord blood units

Human leucocyte antigen (HLA) alleles and haplotypes differ significantly among different ethnic groups, and high‐resolution typing methods allow for the detection of a wider spectrum of HLA variations. In this study, HLA‐A, ‐B and ‐DRB1 genotypes were analysed in 4128 cord blood units obtained from Korean women using the sequence‐based typing method. A total of 44 HLA‐A, 67 HLA‐B and 48 HLA‐DRB1 most probable alleles were identified. Of these, high‐frequency alleles found at a frequency of ≥5% were 6 HLA‐A (A*02:01, A*02:06, A*11:01, A*24:02, A*31:01, A*33:03), 5 HLA‐B (B*15:01, B*44:03, B*51:01, B*54:01, B*58:01) and 7 HLA‐DRB1 (DRB1*01:01, DRB1*04:05, DRB1*07:01, DRB1*08:03, DRB1*09:01, DRB1*13:02, DRB1*15:01) alleles. At each locus, A*02, B*15 and DRB1*04 generic groups were most diverse at allelic level, consisting of 8, 11 and 10 different alleles, respectively. Two‐ and three‐locus haplotypes estimated by the maximum likelihood method revealed 73 A‐B, 74 B‐DRB1 and 42 A‐B‐DRB1 haplotypes with frequencies of ≥0.3%. A total of 193 A‐B‐DRB1 haplotypes found at a frequency of ≥0.1% were presented, and the six most common haplotypes were A*33:03‐B*44:03‐DRB1*13:02 (4.6%), A*33:03‐B*58:01‐DRB1*13:02 (3.0%), A*24:02‐B*07:02‐DRB1*01:01 (2.7%), A*33:03‐B*44:03‐DRB1*07:01 (2.5%), A*30:01‐B*13:02‐DRB1*07:01 (2.2%) and A*24:02‐B*52:01‐DRB1*15:02 (2.1%). Compared with previous smaller scale studies, this study further delineated the allelic and haplotypic diversity in Koreans including low‐frequency alleles and haplotypes. Information obtained in this study will be useful for the search for unrelated bone marrow donors and for anthropologic and disease association studies.     

Characterization of a novel MICA allele,MICA*012:05, by cloning and sequencing

A new MICA allelic variant, MICA*012:05, has been identified in a Chinese Mongolian population. Following polymerase chain reaction–sequence‐based typing (PCR‐SBT), this new allele was further confirmed by cloning and sequencing. MICA*012:05 was linked to an HLA‐A*24‐C*01‐B*55:02‐DRB1*09 haplotype. MICA*012:05 differs from MICA*012:01 by a single synonymous C to T substitution at nucleotide position 269 in exon 3.     

Association of MICA and HLA‐B alleles with leprosy in two endemic populations in Brazil

Leprosy is a prevalent disease in Brazil, which ranks as the country with the second highest number of cases in the world. The disease manifests in a spectrum of forms, and genetic differences in the host can help to elucidate the immunopathogenesis. For a better understanding of MICA association with leprosy, we performed a case–control and a family‐based study in two endemic populations in Brazil. MICA and HLA‐B alleles were evaluated in 409 leprosy patients and in 419 healthy contacts by PCR‐SSOP‐Luminex‐based technology. In the familial study, analysis of 46 families was completed by direct sequencing of all exons and 3′/5′untranslated regions, using the Ilumina MiSeq platform. All data were collected between 2006 and 2009. Statistical analysis was performed using the Chi‐square or Fisher's exact test together with a multivariate analysis. Family‐based association was assessed by transmission disequilibrium test (TDT) software FBAT 2.0.4. We found associations between the haplotype MICA*002‐HLA‐B*35 with leprosy in both the per se and the multibacillary (MB) forms when compared to healthy contacts. The MICA allele *008 was associated with the clinical forms of paucibacillary (PB). Additionally, MICA*029 was associated with the clinical forms of MB. The association of MICA*029 allele (MICA‐A4 variant) with the susceptibility to the MB form suggests this variant for the transmembrane domain of the MICA molecule may be a risk factor for leprosy. Two MICA and nine HLA‐B variants were found associated with leprosy per se in the Colônia do Prata population. Linkage disequilibrium analysis revealed perfect linkage disequilibrium (LD) between HLA‐B markers rs2596498 and rs2507992, and high LD (R² = .92) between these and the marker rs2442718. This familial study demonstrates that MICA association signals are not independent from those observed for HLA‐B. Our findings contribute the knowledge pool of the immunogenetics of Hansen's disease and reveals a new association of the MICA*029 allele.     

MICA polymorphism in a sample of the São Paulo population,Brazil

The major histocompatibility complex (MHC) class I chain‐related A (MICA) gene, located near HLA‐B, codes for protein products with structural similarities to those of classical MHC class I genes, but which neither bind β₂‐microglobulin nor present peptide. Expressed predominantly on gastrointestinal and tumour epithelial cells, they are stress‐induced and interact with C‐type lectin like receptor (NKG2D) on γδ, αβ CD8+ T cells and natural killer (NK) cells. MICA is highly polymorphic, with 54 extracellular allelic sequences described. We typed 200 healthy subjects in a sample of the São Paulo population by extended polymerase chain reaction–sequence‐specific primers (PCR‐SSP) to characterize the MICA polymorphism and analysed MICA/HLA‐B linkage disequilibrium. The MICA*008 group (g) was predominant (47%), with several HLA‐B associations. Rare combinations MICA*008g‐HLA‐B37, MICA*008g‐B72 and MICA*010‐HLA‐B52 were detected. Given the extent of this polymorphism and its possible relevance for disease association, we determined MICA and HLA‐B alleles in 33 Behçet's patients, in an attempt to clarify the associated genetic marker. Our results showed an increase of MICA*006, but not MICA*009, in the patient group (6/33) compared with controls (3/200) (18.2% vs. 1.5%; P_c = 0.005). Both alleles were always in association with HLA‐B51, suggesting that HLA‐B is indeed the primary susceptibility locus (P = 0.00008) and that MICA*006 may be an additional risk factor.     

MICB polymorphism in a southern Chinese Han population: the identification of two new MICB alleles, MICB*005:06 and MICB*026

In this study, we investigated the major histocompatibility complex (MHC) class I chain-related gene B (MICB) allelic variation by sequence-based typing (SBT) in 201 healthy, unrelated Han subjects from Hunan province, southern China. Eleven MICB alleles were observed, among which MICB^∗005:02 predominated with a frequency of 64.93%. Significant linkage disequilibrium (LD) was observed for 5 HLA-B-MICB and 6 MICA-MICB haplotypes. Compared with a northern Chinese Han population, several MICB-containing haplotypes appeared to be highly specific to this southern Chinese Han population. Two new MICB alleles, MICB^∗005:06 and MICB^∗026, were identified. Aligned with MICB^∗005:02, MICB^∗005:06 has a synonymous T replacement at nucleotide 762 in exon 4; MICB^∗026 has probably arisen from MICB^∗004:01 through a single nucleotide substitution from G to A at position 826 in exon 4, leading to an amino acid change from glutamic acid to lysine at codon 253. HLA-A^∗02-C^∗01-B^∗46-MICA^∗010-MICB^∗005:02-DRB1^∗09 was the most prevalent six-locus haplotype with a frequency of 8.49%. HLA-A^∗30-C^∗06-B^∗13:02-MICA^∗008:01-MICB^∗005:02-DRB1^∗07 appeared to be a conserved extended haplotype. Our results provide new information about MICB genetic polymorphism in Chinese Han populations, and will inform future studies of the potential role of MICB in allogeneic organ transplantation and disease susceptibility in related ethnic groups.     

HLA‐A,HLA‐B and HLA‐DRB1 allele and haplotype frequencies of 10 918 Koreans from bone marrow donor registry in Korea

The human leucocyte antigen (HLA) system is the most polymorphic genetic system in humans, and HLA matching is crucial in organ transplantation, especially in hematopoietic stem cell transplantation. We investigated HLA‐A, HLA‐B and HLA‐DRB1 allele and haplotype frequencies at allelic level in 10 918 Koreans from bone marrow donor registry in Korea. Intermediate resolution HLA typing was performed using Luminex technology (Wakunaga, Japan), and additional allelic level typing was performed using PCR–single‐strand conformation polymorphism method and/or sequence‐based typing (Abbott Molecular, USA). Allele and haplotype frequencies were calculated by direct counting and maximum likelihood methods, respectively. A total of 39 HLA‐A, 66 HLA‐B and 47 HLA‐DRB1 alleles were identified. High‐frequency alleles found at a frequency of ≥5% were 6 HLA‐A (A*02:01, *02:06, *11:01, *24:02, *31:01 and *33:03), 6 HLA‐B (B*15:01, *35:01, *44:03, *51:01, 54:01 and *58:01) and 8 HLA‐DRB1 (DRB1*01:01, *04:05, *04:06, *07:01, *08:03, *09:01, *13:02 and *15:01) alleles. At each locus, A*02, B*15 and DRB1*14 generic groups were most diverse at allelic level, consisting of 9, 12 and 11 different alleles, respectively. A total of 366, 197 and 21 different HLA‐A‐B‐DRB1 haplotypes were estimated with frequencies of ≥0.05%, ≥0.1% and ≥0.5%, respectively. The five most common haplotypes with frequencies of ≥2.0% were A*33:03‐B*44:03‐DRB1*13:02 (4.97%), A*33:03‐B*58:01‐DRB1*13:02, A*33:03‐B*44:03‐DRB1*07:01, A*24:02‐B*07:02‐DRB1*01:01 and A*24:02‐B*52:01‐DRB1*15:02. Among 34 serologic HLA‐A‐B‐DR haplotypes with frequencies of ≥0.5%, 17 haplotypes revealed allele‐level diversity and majority of the allelic variation was arising from A2, A26, B61, B62, DR4 and DR14 specificities. Haplotype diversity obtained in this study is the most comprehensive data thus far reported in Koreans, and the information will be useful for unrelated stem cell transplantation as well as for disease association studies.     

Identification of a novel MICB allele,MICB*030, by cloning and sequencing

A novel MICB allele, MICB*030, has been identified in a healthy Chinese individual of Mongol ethnicity residing in northern China by polymerase chain reaction sequence‐based typing (PCR‐SBT) and confirmed by cloning and sequencing. MICB*030 was linked to HLA‐B*35. Aligned with MICB*005:02, MICB*030 has a nonsynonymous adenine substitution at nucleotide position 50 in exon 3, leading to amino acid change from serine to arginine at codon 102 of the mature MICB molecule.     

The distribution of MICA alleles in an Austrian population: Evidence for increasing polymorphism

The Major Histocompatibility Complex Class I Chain-Related Gene A (MICA) is located 46.4 Kb centromeric to HLA-B locus on chromosome 6; 84 alleles have been described so far. To assess the distribution of MICA alleles in an Austrian population, 322 unrelated Austrian blood donors have been typed for MICA by direct sequencing of amplified exons 2–5; sequencing of exon 6 and separating alleles by haplotype specific primers or by cloning was performed to resolve ambiguities. HLA-B was typed at low level resolution and linkage disequilibrium was determined. We observed 20 already known and four novel MICA alleles. MICA^∗008:01/04 was the most frequent allele (42%), followed by MICA^∗002:01 (11%) and MICA^∗009:01 (9%), three alleles (MICA^∗029, ^∗067 and ^∗068) were observed only once. No deviation from the Hardy Weinberg equilibrium was observed. Linkage disequilibrium between MICA and HLA-B alleles was observed, most extensively between MICA^∗008:01/04 and HLA-B^∗07. Our population data are in agreement with other European populations. The fact that four novel alleles have been observed indicates that the polymorphism of MICA is larger than currently estimated.     

HLA class I chain-related MICA and MICB genes polymorphism in healthy individuals from the Bulgarian population

Although human leukocyte antigen (HLA) gene polymorphism has been investigated in many populations around the world, the data on MHC class I chain-related (MIC) genes are still limited. The present study is aimed to analyze the allelic polymorphism of MICA and MICB genes and haplotype associations with HLA-B locus in 132 healthy, unrelated individuals from the Bulgarian population by next generation sequencing (NGS). A total of 36 MICA and 16 MICB alleles were observed with the highest frequency detected for MICA*008:01 (17.1%) and MICB*005:02 (32.4%). Further, two and three-loci haplotype frequencies and pairwise linkage disequilibrium were estimated. Highly significant global linkage disequilibrium was found between either HLA-B and MICA and MICB genes. This is the first study on MICA and MICB allelic polymorphism, linkage disequilibrium, and haplotype polymorphism in the Bulgarian population. These results will allow for better characterization of the genetic heterogeneity of the Bulgarian population and could contribute to further analyses on MICA and MICB clinical significance.     

Distribution of MICA alleles and haplotypes associated with HLA-B in Greek population

IntroductionThe Major Histocompatibility Complex Class I-related chain A gene (MICA) is a highly polymorphic functional gene located close to the HLA-B locus. Certain MICA alleles have been related to inflammatory and autoimmune diseases while MICA antibodies have been implicated in organ allograft rejection or graft-versus-host disease (GVHD).AimThe aim of this study was to identify the frequencies of MICA alleles and MICA ~ HLA-B haplotypes in the Greek population since, as far as we know, these data are still limited.MethodsDNA was obtained from 277 unrelated healthy Greek individuals of Caucasian origin, volunteer donors of blood stem cells. HLA-B* and MICA* genotyping was performed by reverse PCR-SSOP.ResultsA total of 18 MICA alleles were defined in the present study. The five most frequent alleles in the Greek population were MICA*008 (24.6%), MICA*009 (22.36%), MICA*018 (16.03%), MICA*002 (8.02%) and MICA*004 (7.17%) which altogether account for 77.8% of all alleles. The most common MICA ~ HLA-B haplotypes were MICA*018 ~ B*18 (12.5%) and MICA*009 ~ B*51(11.5%).ConclusionsThe five most frequent MICA alleles in the Greek population were *008, *009, *018, *002, *004. In other Caucasian populations, two of these alleles (*008, and *004) were observed in similar frequencies. MICA*002 was observed less frequently (8.02%) in the Greek population compared to other Caucasian groups (frequencies > 15%). Also, MICA*009 and MICA*018 had elevated frequencies (above 15%) whereas in other Caucasian populations they were found around 10% or less. These data may be important for the elucidation of the role that MICA polymorphisms play in organ and stem cell transplantation and to identify the relation of certain MICA with susceptibility to specific diseases.     

Allelic diversity and affinity variants of MICA are imbalanced in Spanish patients with Behçet's disease

The aetiology of Behçet's disease (BD) is still unknown, but genetic and environmental factors are involved. HLA‐B*51 is considered a susceptibility marker and some MICA alleles have also been associated. Cytotoxic T lymphocytes have been suggested as responsible for BD lesions by engaging MICA through NKG2D surface molecules. In the present study, HLA‐B and MICA alleles were typed by polymerase chain reaction using sequence‐specific primers, in 165 healthy Spanish controls and 42 BD patients. In the healthy group, MICA*008 (28.48%), MICA*004 (17.58%), MICA*002 (14.24%) and MICA*009 (9.39%) were the predominant alleles and the most common haplotype was MICA*004‐B*44 (12.12%). MICA*001 (5.15%), MICA*004, MICA*011 (4.54%) and MICA*018 (5.15%) were more frequent, and MICA*010 (1.81%) and MICA*008 were less prevalent than in other Caucasoid populations. Similar results have been reported in North African individuals and this could support the hypothesis of a common ancestral origin of both populations. The frequencies of MICA*009 and MICA*019 were significantly increased in our BD patients in comparison with controls: 22.62% versus 9.39% and 10.71% versus 1.81% respectively. The increase of MICA*019 had not been described in other BD cohorts, and it corroborates the genetic heterogeneity at MICA locus in BD patients. High‐affinity MICA alleles for NKG2D were more frequent in controls than in patients. Moreover, high‐affinity alleles were not found in homozygous BD patients. These results argue against the hypothesis of an autoaggressive response in BD patients through MICA–NKG2D interactions.     

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

A new MICA allelic variant, MICA*007:07, was identified in an individual of Mongol ethnicity in the Inner Mongolia Autonomous Region, northern China. Following polymerase chain reaction‐sequence‐based typing (PCR‐SBT), this new allele was further confirmed by cloning and sequencing. MICA*007:07 differs from MICA*007:01 by a synonymous mutation from G to A at the 2nd nucleotide position in exon 2. MICA*007:07 was linked to HLA‐B*27:05.     

HLA‐A, ‐B and ‐DRB1 allele and haplotype frequencies of 8333 Chinese Han from the Zhejiang province,China

The distribution of human leucocyte antigen (HLA) allele and haplotype is varied among different ethnic populations. In this study, HLA‐A, ‐B and ‐DRB1 allele and haplotype frequencies were determined in 8333 volunteer bone marrow donors of Zhejiang Han population using the polymerase chain reaction sequence‐based typing. A total of 52 HLA‐A, 96 HLA‐B and 61 HLA‐DRB1 alleles were found. Of these, the top three frequent alleles in HLA‐A, HLA‐B and HLA‐DRB1 loci, respectively, were A*11:01 (24.53%), A*24:02 (17.35%), A*02:01 (11.58%); B*40:01 (15.67%), B*46:01 (11.87%), B*58:01 (9.05%); DRB1*09:01 (17.54%),DRB1*12:02 (9.64%) and DRB1*08:03 (8.65%). A total of 171 A‐B‐DRB1 haplotypes with a frequency of >0.1% were presented and the five most common haplotypes were A*33:03‐B*58:01‐ DRB1*03:01, A*02:07‐B*46:01‐DRB1*09:01, A*30:01‐B*13:02‐DRB1*07:01, A*33:03‐B*58:01‐RB1*13:02 and A*11:01‐B*15:02‐DRB1*12:02. The information will be useful for selecting unrelated bone marrow donors and for anthropology studies and pharmacogenomics analysis.     

MHC class I chain-related gene B promoter polymorphisms and celiac disease

The possibility that susceptibility to celiac disease (CD) might be influenced by the MHC class I chain-related gene family, MICA and MICB, has been previously reported. In this study, we analyzed the MICB promoter and examined the association of the polymorphisms found within such in a group of CD patients. To study the MICB promoter we sequenced the 5' flanking region of MICB gene in DNA from homozygous B-lymphoblastoid cell lines corresponding to the most frequent MICB alleles found in our population (MICB*00502, MICB*002, MICB*004, and MICB*008). DNA from a MICB*003 homozygous individual was also analyzed. Sequence analysis revealed six single nucleotide polymorphisms located at positions 45860 C/A, 45862 G/C, 45877 C/G, 46113 A/C, 46219 G/C, and 46286 G/C and an insertion of 2 bp --/AG at position 45944 according to the published genomic sequence. Those polymorphisms were found to be associated in four different haplotypes corresponding to different MICB alleles. Subsequently, 126 CD subjects and 117 healthy controls were typed by polymerase chain reaction using sequence-specific primers for these polymorphisms. MICB promoter polymorphism haplotypes were also found in our population and showed strong linkage disequilibrium with MICB alleles. MICB promoter polymorphism Haplotype 3, included in MICB*002 and MICB*008 alleles, was found to be overrepresented in CD patients (79.4% CD patients vs 45.3% healthy controls; p(c) < 0.0001; OR = 4.64; CI 95% = 2.64-8.16). Both MICB*008 and MICB*002 alleles were found as part of the CD susceptibility extended haplotypes B8/DR3/DQ2, B18/DR3/DQ2, and DR4/DQ8.