Immunogenetics of three novel HLA‐Class II alleles: DRB1*03:112, DQB1*03:02:16 and DQB1*03:139

Three novel HLA‐Class II alleles, DRB1*03:112, DQB1*03:02:16 and DQB1*03:139, are described with predicted bearing haplotypes of A*02:01, B*40:01, C*03:04, DRB1*03:112, DQB1*02:01; A*23:01, B*15:01, C*03:03, DRB1*04:01, DQB1*03:02:16 and A*01:01, B*44:02, C*05:01/03, DRB1*04:01, DQB1*03:139. Serological tests showed that the DRB1*03:112 and DQB1*03:139 specificities failed to react as expected with some well‐documented monoclonal antibodies. Subsequent examination of published HLA‐Class II epitopes and inspection of amino acid motifs suggested that epitopes exist that include the positions of their single substitutions (F31C between DRB1*03:01:01:01 and DRB1*03:112, and R48P between DQB1*03:01:01:01 and DQB1*03:139 specificities). This suggests that the reactivity of the monoclonal antibodies used was dependent on these epitopes and that their loss from these rare allele products resulted in their aberrant serology. The new alleles were found after the sequence‐based typing of 32 530 random UK European routine blood donors suggesting that each has a maximum carriage frequency of 0.0031% in the blood donor population resident in Wales.     

HLA‐A,HLA‐B and HLA‐DRB1 allele and haplotype diversity among volunteer bone marrow donors from Croatia

The determination of human leucocyte antigen (HLA)‐A, HLA‐B and HLA‐DRB1 alleles in the routine procedure of a volunteer hematopoietic stem cell (HSC) donor's registration in the Croatian Bone Marrow Donor Registry (CBMDR) is performed to enhance the odds of finding a suitable HLA compatible donor for patients in need of a HSC transplantation worldwide. However, besides its original purpose, it also provides valuable information about the HLA polymorphism among Croats. The aim of the present study was to analyse the HLA allele and haplotype frequencies in a sample of 4000 donors from CBMDR. The distribution of HLA‐A, HLA‐B and HLA‐DRB1 alleles did not demonstrate significant differences from the data reported for other European populations. The higher frequency of B*40:02 allele in comparison with B*40:01 and DRB1*11:04 in comparison with DRB1*11:01 is interesting because it represents a difference in comparison with the Western and Northern European populations which are a main source of donors for Croatian patients. The haplotype frequencies show a greater variation and difference in comparison with data from other registries and populations; however, due to a lack of high‐resolution haplotype data, comparison was possible only with a very limited number of other populations.     

Identification of the novel HLA‐B*40:221 allele in a Taiwanese hematopoietic stem cell donor using a sequence‐based typing method

Using DNA sequence‐based typing method, we found a new HLA‐B*40 variant, B*40:221, in a Taiwanese hematopoietic stem cell donor. The allele sequence of B*40:221 is identical to the sequence of B*40:01:01 in exons 2, 3 and 4 except the nucleotides at codon 265 (GGG→AGG). The sequence variation caused one amino acid exchange at residue 265 where Gly was replaced by Arg. The probable HLA‐A, ‐B, ‐C, ‐DRB1 and ‐DQB1 haplotype in association with B*40:221 may be deduced as HLA‐A*11:01‐B*40:221‐C*03:04‐DRB1*14:54‐DQB1*05:02. The generation of B*40:221 is thought as a result of a nucleotide point mutation involving B*40:01:01. Our discovery of B*40:221 increases the polymorphism of B*40 in Taiwanese.     

Detection of the rare HLA‐B*40:97 allele in an unrelated Taiwanese bone marrow donor

We detected a rare HLA‐B locus allele, B*40:97, in a Taiwanese unrelated donor in our routine HLA SBT (sequence‐based typing) exercise for a possible hematopoietic stem cell donation. In exons 2, 3 and 4, the sequence of B*40:97 is identical to the sequence of B*40:02:01 except one nucleotide at nucleotide position 760 (C‐>T) in exon 4. The nucleotide variation caused one amino acid alteration at residue 230 (L‐>F). B*40:97 was probably derived from a nucleotide substitution event where C was replaced by T at nucleotide 760 involving B*40:02:01. The HLA‐A, HLA‐B, HLA‐C, HLA‐DRB1 and HLA‐DQB1 haplotype in association with B*40:97 may be deduced as A*26:01‐B*40:97‐C*03:03‐DRB1*11:01‐DQB1*03:03. Our recognition of B*40:97 in Taiwanese helps to fill the void of ethnic information for the allele B*40:97 reported to the IMGT/HLA Database.     

Discovery of a novel HLA‐DRB1*04:05 variant,DRB1*04:05:15, in a Taiwanese and the probable HLA haplotype in association with DRB1*04:05:15

Here, we report a novel HLA‐DRB1*04 allele, DRB1*04:05:15, found in a Taiwanese unrelated volunteer bone marrow hematopoietic stem cell donor by a sequence‐based typing (SBT) method. The DNA sequence of DRB1*04:05:15 is identical to the sequence of DRB1*04:05:01 in exon 2, except the nucleotide at the position 198 where C is substituted by T (TAC→TAT at codon 37). Due to the silent mutation, the nucleotide replacement generated no amino acid variation in comparison with DRB1*04:05:01. We postulate the allele DRB1*04:05:15 was probably derived from DRB1*04:05:01 via a nucleotide point mutation event. The probable HLA‐A, ‐B, ‐C, ‐DRB1 and ‐DQB1 haplotype in association with DRB1*04:05:15 may be deduced as A*02:01‐B*48:01‐C*08:03‐DRB1*04:05:15‐DQB1*04:01.     

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.     

High susceptibility to pemphigus vulgaris due to HLA‐DRB1*14:54 in the Slovak population

The current work describes an association between pemphigus vulgaris (PV) and class II HLA alleles in the Slovak population, the first such study in Slovakia on the ‘high‐resolution level’. This work takes into account the new HLA allele nomenclature, officially adopted in 2010. In particular, we have focused on the associations between PV and DRB1*14:54 and DRB1*14:01. This case–control study was performed in a cohort of 43 PV Caucasian patients and 113 Caucasian control subjects from Slovakia. HLA typing was performed using PCR‐SSP (polymerase chain reaction with sequence‐specific primers). We found significantly positive associations between PV and the HLA alleles DRB1*04:02, DRB1*04:04, DRB1*14:54, DRB1*14:04, DRB1*14:05, DQB1*03:02 and DQB1*05:03. In contrast, HLA‐DQB1*06, DRB1*07 and DRB1*13 were negatively associated with PV. Importantly, 93% of PV patients possessed at least one of two HLA haplotypes, DRB1*04–DQB1*03 or HLA‐DRB1*14–DQB1*05. We confirmed the previously reported associations between HLA class II alleles and PV and described a new association between PV and DRB1*14:54. This allele was first described in 2005, and there has been only one report of its association with PV to date.     

Discovery of the novel HLA‐DRB1*10:04 allele in a Taiwanese volunteer bone marrow donor and identification of the probable HLA‐A, ‐B, ‐C and ‐DRB1 haplotype in association with DRB1*10:04

We report here a novel variant of HLA‐DRB1*10, DRB1*10:04, discovered in a Taiwanese volunteer bone marrow donor by a sequence‐based typing (SBT) method. The DNA sequence of DRB1*10:04 differs from DRB1*10:01:01, in exon 2, at nucleotide positions 296 (G→A) and 303 (T→G). The nucleotide changes caused an amino acid substitution at amino acid residue 70 (R→Q). We hypothesize that the formation of DRB1*10:04 was probably the result of a gene recombination event where DRB1*10:01:01 received a minimum length of DNA sequence from DRB1*04:05:01, as the sequence of DRB1*10:04 is identical to DRB1*10:01:01 in exon 2 except the sequence from nucleotide 296 to nucleotide 303, which is identical to DRB1*04:05:01. The plausible HLA‐A, ‐B, ‐C and ‐DRB1 haplotypes in association with DRB1*10:04 was deduced as A*01:01‐B*37:01‐C*06:02‐DRB1*10:04.     

Frequencies of allele groups HLA‐A,HLA‐B and HLA‐DRB1 in a population from the northwestern region of São Paulo State,Brazil

The aim of this study was to estimate the HLA‐A, HLA‐B and HLA‐DRB1 allele groups frequencies in a population of 1559 volunteer bone marrow donors from the northwestern region of São Paulo State grouped according to ethnicity. An additional objective was to compare the allele frequencies of the current study with data published for other Brazilian populations. The allele groups were characterized by the PCR‐rSSO method using Luminex^® technology. Twenty HLA‐A, 32 HLA‐B and 13 HLA‐DRB1 allele groups were identified. The most common allele groups in European descent and mixed African and European descent samples were HLA‐A*02, HLA‐B*35 and HLA‐DRB1*13, while HLA‐A*02, HLA‐B*35 and HLA‐DRB1*11 were more common in African descent samples. The HLA‐A*23, HLA‐A*36, HLA‐B*58 and HLA‐B*81 allele groups were more common in sample from African descent than European descent, and the HLA‐DRB1*08 was more common in mixed African and European descent than in European descent. Allele group frequencies were compared with samples from other Brazilian regions. The HLA‐A*30 and HLA‐A*23 were more common in this study than in the populations of Rio Grande do Sul and Paraná; and the HLA‐A*01, HLA‐B*18, HLA‐B*57 and HLA‐DRB1*11 were more common in this study than in the population of Piauí. The least frequent allele groups were HLA‐A*31, HLA‐B*15, HLA‐B*40 and HLA‐DRB1*08 for the population of Piauí, HLA‐A*01 and HLA‐A*11 for Parana, HLA‐A*02 and ‐A*03 for Rio Grande do Sul and HLA‐DRB1*04 for Paraná, Rio Grande do Sul and Piauí. These data provide an overview on the knowledge on HLA diversity in the population of the northwestern region of São Paulo State and show that the genes of this system are useful to distinguish different ethnic groups.     

The distributions of HLA‐A,HLA‐B,HLA‐C,HLA‐DRB1 and HLA‐DQB1 allele and haplotype at high‐resolution level in Zhejiang Han population of China

The distributions of HLA allele and haplotype are variable in different ethnic populations and the data for some populations have been published. However, the data on HLA‐C and HLA‐DQB1 loci and the haplotype of HLA‐A, HLA‐B, HLA‐C, HLA‐DRB1 and HLA‐DQB1 loci at a high‐resolution level are limited in Zhejiang Han population, China. In this study, the frequencies of the HLA‐A, HLA‐B, HLA‐C, HLA‐DRB1 and HLA‐DQB1 loci and haplotypes were analysed among 3,548 volunteers from the Zhejiang Han population using polymerase chain reaction sequencing‐based typing method. Totals of 51 HLA‐A, 97 HLA‐B, 45 HLA‐C, 53 HLA‐DRB1 and 27 HLA‐DQB1 alleles were observed. The top three frequent alleles of HLA‐A, HLA‐B, HLA‐C, HLA‐DRB1 and HLA‐DQB1 loci were A*11:01 (23.83%), A*24:02 (17.16%), A*02:01 (11.36%); B*40:01 (14.08%), B*46:01 (12.20%), B*58:01 (8.50%); C*07:02 (18.25%), C*01:02:01G (18.15%), C*03:04 (9.88%); DRB1*09:01 (17.52%), DRB1*12:02 (10.57%), DRB1*15:01 (9.70%); DQB1*03:01 (22.63%), DQB1*03:03 (18.26%) and DQB1*06:01 (10.88%), respectively. A total of 141 HLA‐A‐C‐B‐DRB1‐DQB1 haplotypes with a frequency of ≥0.1% were found and the haplotypes with frequency greater than 3% were A*02:07‐C*01:02:01G‐B*46:01‐DRB1*09:01‐DQB1*03:03 (4.20%), A*33:03‐C*03:02‐B*58:01‐DRB1*03:01‐DQB1*02:01 (4.15%), A*30:01‐C*06:02‐B*13:02‐DRB1*07:01‐DQB1*02:02 (3.20%). The likelihood ratios test for the linkage disequilibrium of two loci haplotypes was revealed that the majority of the pairwise associations were statistically significant. The data presented in this study will be useful for searching unrelated HLA‐matched donor, planning donor registry and for anthropology studies in China.     

A conserved HLA‐A*02:28 associated HLA haplotype,A*02:28‐B*15:11‐DRB1*09:01, restricted to Taiwanese

HLA‐A*02:28, found in a Korean and a Japanese, was reported independently to the IMGT/HLA database in 2003 and 2005, respectively. We report here eight Taiwanese unrelated bone marrow hematopoietic stem cell donors carrying A*02:28 detected during our routine HLA typing exercise. The probable HLA‐A, ‐B and ‐DRB1 haplotype in association with A*02:28 may be deduced from the eight marrow stem cell donor as A*02:28‐B*15:11‐DRB1*09:01. Our result suggests A*02:28‐B*15:11‐DRB1*09:01 is a conserved HLA haplotype restricted to Taiwanese.     

Two novel alleles HLA‐DRB1*11:150 and HLA‐DRB1*14:145 identified in Saudi individuals

Two new HLA‐ DRB1 alleles were identified by sequence‐based typing method (SBT) in 1100 participants in the Saudi Stem Cell Donor Registry. HLA‐DRB1*11:150 differs from HLA‐DRB1*11:01:01G by a single C to A substitution at nucleotide position 5580 in exon 2, resulting in an amino acid change from alanine to glutamic acid at position 74. HLA‐DRB1*14:145 differs from HLA‐DRB1*14:04 by a C to G substitution at nucleotide position 5511 in exon 2, resulting in an amino acid change from threonine to arginine at position 51.     

Discovery of the novel HLA‐DRB1*04:05:14 allele in a Taiwanese unrelated haematopoietic stem cell donor by a sequence‐based typing method

We report here a de novo HLA‐DRB1*04 allele, DRB1*04:05:14, discovered in a Taiwanese unrelated volunteer bone marrow stem cell donor by a sequence‐based typing method. In exon 2, the DNA sequence of DRB1*04:05:14 is identical to the sequence of DRB1*04:05:01 except the nucleotide at positions 321 where C is replaced by T (at codon 78; TAC→TAT). Due to the silent mutation, the nucleotide substitution produced no amino acid variation in comparison with DRB1*04:05:01. We assume DRB1*04:05:14 was derived from DRB1*04:05:01 via a point mutation. The probable HLA‐A, ‐B and ‐DRB1 haplotype in association with DRB1*04:05:14 may be deduced as A*11‐B*55‐DRB1*04:05:14. We here report the Taiwanese ethnicity of DRB1*04:05:14.     

Study on the polymorphisms of HLA‐ABCDQB1DRB1 alleles and haplotypes in Hubei Han population of China

The present study aimed to analyse the frequencies of human leukocyte antigen HLA‐ABCDQB1 and HLA‐DRB1 alleles and haplotypes in a subset of 3,732 Han population from Hubei of China. All samples were typed in the HLA‐ABCDQB1 and HLA‐DRB1 loci using the sequence‐based typing method; subsequently, the HLA polymorphisms were analysed. A total of 47 HLA‐A, 89 HLA‐B, 43 HLA‐C, 49 HLA‐DRB1 and 24 HLA‐DQB1 alleles were identified in the Hubei Han population. The top three most frequent alleles in the HLA‐ABCDQB1 and HLA‐DRB1 were A*11:01 (0.2617), A*24:02 (0.1590), A*02:07 (0.1281); B*46:01 (0.1502), B*40:01 (0.1409) and B*58:01 (0.0616); C*01:02 (0.2023), C*07:02 (0.1691) and C*03:04 (0.1175); and DQB1*03:01 (0.2000), DQB1*03:03 (0.1900), DQB1*06:01 (0.1187); DRB1*09:01 (0.1790), DRB1*15:01 (0.1062) and DRB1*12:02 (0.0841), respectively. Meanwhile, the three most frequent two‐loci haplotypes were A*02:07‐C*01:02 (0.0929), B*46:01‐C*01:02 (0.1366) and DQB1*03:03‐DRB1*09:01 (0.1766). The three most frequent three‐loci haplotypes were A*02:07‐B*46:01‐C*01:02 (0.0883), B*46:01‐DQB1*03:03‐DRB1*09:01 (0.0808) and C*01:02‐DQB1*03:03‐DRB1*09:01 (0.0837). The three most frequent four‐loci haplotypes were A*02:07‐B*46:01‐C*01:02‐DQB1*03:03 (0.0494), B*46:01‐DRB1*09:01‐C*01:02‐DQB1*03:03 (0.0729) and A*02:07‐B*46:01‐DQB1*03:03‐DRB1*09:01 (0.0501). The most frequent five‐loci haplotype was A*02:07‐B*46:01‐C*01:02‐DQB1*03:03‐DRB1*09:01 (0.0487). Heat maps and multiple correspondence analysis based on the frequencies of HLA specificity indicated that the Hubei Han population might be described into Southern Chinese populations. Our results lay a certain foundation for future population studies, disease association studies and donor recruitment strategies.     

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 the novel HLA‐B*13:02:13 allele in a Taiwanese haematopoietic stem cell donor and the probable HLA haplotype in association with B*13:02:13

Using sequence‐based typing method, we found a new HLA‐B*13:02 variant, B*13:02:13, in a Taiwanese haematopoietic stem cell donor. The DNA sequence of B*13:02:13 is identical to the sequence of B*13:02:01 in exons 2 and 3 except the nucleotide at position 588 where G is replaced by T (codon 172; CTG→CTT). The DNA sequence variation did not alter the amino acid sequence of B*13:02:01. The generation of B*13:02:13 is thought to derive from B*13:02:01 as a result of a silence mutation. The probable HLA‐A, HLA‐B and HLA‐DRB1 haplotype in association with B*13:02:1 may be deduced as HLA‐A*24‐B*13:02:13‐DRB1*07:01 or HLA‐A*02‐B*13:02:13‐DRB1*07:01. The discovery of B*13:02:13 furthers the polymorphism of HLA‐B*13 and HLA‐B*13:02.     

Heterogeneity of HLA-DRB1*04 alleles and haplotypes in the Croatian population

Analysis of allele distribution at the HLA-DRB1*04 gene, as one of the frequent ones among Croatians, and their HLA-A-B-DRB1 haplotypes in the Croatian population was performed in this study. Using LABType(?) SSO and PCR-SSP method, 11 DRB1*04 subtypes were observed, of which DRB1*04:01 was the most frequent (28.0%) followed by DRB1*04:02 (26.3%), DRB1*04:03 (22.3%), and DRB1*04:04 (14.2%). The significant haplotypes (with highest P value) for given DRB1*04 allele were the following combinations: HLA-B*15:01-DRB1*04:01, HLA-B*38:01-DRB1*04:02, HLA-B*35:03-DRB1*04:03, HLA-B*35:03-DRB1*04:08, HLA-B*14:01-DRB1*04:04, and HLA-B*49-DRB1*04:05. Marked differences in the distribution of our most frequent haplotypes of HLA-B-DRB1*04 (HLA-B*38:01-DRB1*04:02 and HLA-B*15:01-DRB1*04:01) were found in comparison to other European populations investigated so far. Additionally, comparison of HLA-A-B-DRB1*04 haplotypes showed that although there are similarities in the haplotype structure between our and other populations, there are also noteworthy differences. In summary, the identification of conserved and unusual DRB1*04 haplotypes in the present study of Croats should have important clinical implications for donor-recipient matching in the hematopoietic stem cell transplantation program, help in the understanding of HLA polymorphisms in different European populations, and also prove to be very useful in the determination of possible susceptibility genes involved in HLA-DRB1*04-associated diseases.     

The genetic contribution of HLA‐DRB5*01:01 to systemic lupus erythematosus in Thailand

Human leucocyte antigen (HLA) study in patients with systemic lupus erythematosus (SLE) has been investigated in various countries, but the results are still inconclusive. This study was performed to investigate the association between HLA‐DR and SLE in patients in northern Thailand. HLA‐DR subtyping was performed in 70 patients with SLE and 99 normal healthy controls living in northern Thailand using the INNO‐LiPA HLA‐DR Decoder kit (Innogenetics) and MICRO SSP HLA DNA Typing kit (One Lambda) for reconfirmation. The allele frequency (AF) of DRB5*01:01 in SLE was significantly higher than in the controls [25.7% vs. 14.6%, P = 0.012, Pc = 0.048, OR = 2.02 (95%CI = 1.17–3.48)]. The AF of DRB1*15:01 and DRB1*16:02 showed a nonsignificant tendency to be higher in SLE (10.7% vs. 8.1%, and 17.9% vs. 11.1%). Interestingly, the DRB5*01:01 allele linked to DRB1*16:02 in 47.2% of SLE and 37.9% of controls, and the prevalence of the DRB1*16:02‐DRB5*01:01 haplotype was higher in the patients with SLE [12.1% vs. 5.6%, P = 0.044, OR = 2.35 (95%CI = 1.06–5.19)]. The DRB1*16:02 linked to DRB5*02:02 and *02:03 in 18.2% and 31.8% of controls, respectively, and linked to DRB5*02:03 in 32.0% of SLE patients. The frequency of DRB1*03:01 and *15:02 alleles was not increased in Thai SLE. There was no significant association between DRB5*01:01 and any auto‐antibodies or clinical manifestations of SLE. DRB5*01:01 is associated with Thai SLE, and the association is stronger than that of DRB1*15:01. The genetic contribution of DRB5*01:01 is due partially to the linkage disequilibrium between DRB1*16:02 and DRB5*01:01 in the northern Thai population.     

Human leucocyte antigens class II allele and haplotype association with Type 1 Diabetes in Madeira Island (Portugal)

This study confirms for Madeira Island (Portugal) population the Type 1 Diabetes (T1D) susceptible and protective Human leucocyte antigens (HLA) markers previously reported in other populations and adds some local specificities. Among the strongest T1D HLA associations, stands out, as susceptible, the alleles DRB1*04:05 (OR = 7.3), DQB1*03:02 (OR = 6.1) and DQA1*03:03 (OR = 4.5), as well as the haplotypes DRB1*04:05‐DQA1*03:03‐DQB1*03:02 (OR = 100.9) and DRB1*04:04‐DQA1*03:01‐DQB1*03:02 (OR = 22.1), and DQB1*06:02 (OR = 0.07) and DRB1*15:01‐DQA1*01:02‐DQB1*06:02 (OR = 0.04) as protective. HLA‐DQA1 positive for Arginine at position 52 (Arg52) (OR = 15.2) and HLA‐DQB1 negative for Aspartic acid at the position 57 (Asp57) (OR = 9.0) alleles appear to be important genetic markers for T1D susceptibility, with higher odds ratio values than any single allele and than most of the haplotypes. Genotypes generated by the association of markers Arg52 DQA1 positive and Asp57 DQB1 negative increase T1D susceptibility much more than one would expected by a simple additive effect of those markers separately (OR = 26.9). This study also confirms an increased risk for DRB1*04/DRB1*03 heterozygote genotypes (OR = 16.8) and also a DRB1*04‐DQA1*03:01‐DQB1*03:02 haplotype susceptibility dependent on the DRB1*04 allele (DRB1*04:01, OR = 7.9; DRB1*04:02, OR = 3.2; DRB1*04:04, OR = 22.1).     

Allelic and haplotype diversity of HLA‐A,HLA‐B and HLA‐DRB1 gene at high resolution in the Nanning Han population

The distribution of human leucocyte antigen (HLA) allele and haplotype varied among different ethnic populations. In this study, we investigated the allele and haplotype frequencies of HLA‐A, HLA‐B and HLA‐DRB1 loci in the Nanning Han population who live in Guangxi province of China. We identified 26 HLA‐A, 56 HLA‐B and 31 HLA‐DRB1 alleles in 562 Nanning individuals of Han ethnic group by sequence‐based typing method. Of these, the three most common alleles in HLA‐A, HLA‐B and HLA‐DRB1 loci, respectively, were A*11:01 (32.12%), A*02:07 (12.54%), A*24:02 (12.01%); B*46:01 (14.41%), B*15:02 (13.61%), B*40:01 (11.48%); DRB1*15:01 (14.15%), DRB1*16:02 (11.57%) and DRB1*12:02 (10.14%). With the exception of HLA‐DRB1, the p values of the HLA‐A and HLA‐B loci showed that the HLA allelic distribution in this population was in accordance with Hardy–Weinberg expectation (p > 0.05). A total of 173 HLA~A‐B~DRB1 haplotype with a frequency of >0.1% were presented and the three most common haplotype were HLA‐A*33:03~B*58:01~DRB1*03:01 (6.12%), HLA‐A*11:01~B*15:02~DRB1*12:02 (3.39%) and HLA‐A*11:01~B*15:02~DRB1*15:01 (3.22%). The phylogenetic tree and the principal component analysis suggested that Nanning Han population had a relative close genetic relationship with Chinese Zhuang population and a relative distant genetic relationship with Northern Han Chinese. The information will be useful for anthropological studies, for HLA matching in transplantation and disease association studies in the Chinese population.