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.     

Analysis of high‐resolution HLA‐A, ‐B, ‐Cw, ‐DRB1, and ‐DQB1 alleles and haplotypes in 718 Chinese marrow donors based on donor–recipient confirmatory typings

High‐resolution human leucocyte antigen (HLA)‐A, ‐B, ‐Cw, ‐DRB1, and ‐DQB1 alleles and haplotype frequencies were analysed from 718 Chinese healthy donors selected from the Chinese Marrow Donor Program registry based on HLA donor–recipient confirmatory typings. A total of 28 HLA‐A, 61 HLA‐B, 30 HLA‐Cw, 40 HLA‐DRB1 and 18 HLA‐DQB1 alleles were identified, and HLA‐A*1101, A*2402, A*0201, B*4001, Cw*0702, Cw*0102, Cw*0304, DRB1*0901, DRB1*1501, DQB1*0301, DQB1*0303 and DQB1*0601 were found with frequencies higher than 10% in this study population. Multiple‐locus haplotype analysis by the maximum‐likelihood method revealed 45 A–B, 38 Cw–B, 47 B–DRB1, 29 DRB1–DQB1, 24 A–B–DRB1, 38 A–Cw–B, 23 A–Cw–B–DRB1, 33 Cw–B–DRB1–DQB1 and 22 A–Cw–B–DRB1–DQB1 haplotypes with frequencies >0.5%. The most common two‐, three‐, four‐ and five‐locus haplotypes in this population were: A*0207–B*4601 (7.34%), Cw*0102–B*4601 (8.71%), B*1302–DRB1*0701 (6.19%), DRB1*0901–DQB1*0303 (14.27%), A*3001–B*1302–DRB1*0701 (5.36%), A*0207–Cw*0102–B*4601 (7.06%), A*3001–Cw*0602–B*1302–DRB1*0701 (5.36%), Cw*0602–B*1302–DRB1*0701–DQB1*0202 (6.12%) and A*3001–Cw*0602–B*1302–DRB1*0701–DQB1*0202 (5.29%). Presentation of the high‐resolution alleles and haplotypes data at HLA‐A, ‐B, ‐Cw, ‐DRB1 and ‐DQB1 loci will be useful for HLA matching in transplantation as well as for other medical and anthropological applications in the Chinese population.     

Susceptible and protective associations of HLA DRB1*/DQB1* alleles and haplotypes with ischaemic stroke

Stroke has emerged as the second commonest cause of mortality worldwide and is a major public health problem. For the first time, we present here the association of human leucocyte antigen (HLA)‐DRB1*/DQB1* alleles and haplotypes with ischaemic stroke in South Indian patients. Ischaemic stroke (IS) cases and controls were genotyped for HLA‐DRB1*/DQB1* alleles by polymerase chain reaction sequence‐specific primers (PCR‐SSP) method. The frequencies of HLA class II alleles such as DRB1*04, DRB1*07, DRB1*11, DRB1*12, DRB1*13, DQB1*02 and DQB1*07 were high in IS patients than in the age‐ and gender‐matched controls, suggesting that the individuals with these alleles are susceptible to ischaemic stroke in South India. The frequencies of alleles such as DRB1*03, DRB1*10, DRB1*14, DQB1*04 and DQB1*05 were less in IS cases than in the controls, suggesting a protective association. Haplotypes DRB1*04‐DQB1*0301, DRB1*07‐DQB1*02, DRB1*07‐DQB1*0301, DRB1*11‐DQB1*0301 and DRB1*13‐DQB1*06 were found to be high in IS patients conferring susceptibility. The frequency of haplotype DRB1*10‐DQB1*05 was high in controls conferring protection. IS‐LVD and gender‐stratified analysis too confirmed these susceptible and protective associations. Thus, HLA‐DRB1*/DQB1* alleles and haplotypes strongly predispose South Indian population to ischaemic stroke. Further studies in different populations with large sample size or the meta‐analysis are needed to explain the exact mechanism of associations of HLA gene(s) with IS.     

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.     

Genetic diversity of the HLA system in human populations from the Sierra (Andean), Oriente (Amazonian) and Costa (Coastal) regions of Ecuador

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in a total of 1101 Ecuadorian individuals from three regions of the country, the Coastal region, the Andean region, and the Amazonian region, to obtain information regarding allelic and haplotypic frequencies and their linkage disequilibrium. We find that the most frequent HLA haplotypes with significant linkage disequilibrium in those populations are HLA-A*24～B*35～DRB1*04～DQB1*03:02, A*02～B*35～DRB1*04～DQB1*03:02, A*24～B*35～DRB1*14～DQB1*03:01, A*02～B*35～DRB1*14～DQB1*03:01 and A*02～B*40:02～DRB1*04～DQB1*03:02. The only non-Native American haplotype with frequency >1% shared by all groups was A*29～B*44～DRB1*07～DQB1*02. Admixture estimates obtained by a maximum likelihood method using HLA-B as genetic estimator revealed that the main genetic components for this sample of mixed-ancestry Ecuadorians are Native American (ranging from 52.86% to 63.83%) and European (from 28.95% to 46.54%), while an African genetic component was only apparent in the Coastal region (18.19%). Our findings provide a starting point for the study of population immunogenetics of Ecuadorian populations.     

HLA allele and haplotype frequencies in the Albanian population and their relationship with the other European populations

Human leucocyte antigen (HLA) alleles are very interesting markers in identifying population relationships. Moreover, their frequency distribution data are important in the implementation of donor–recipient registry programs for transplantation purposes and also in determining the genetic predisposition for many diseases. For these reasons, we studied the HLA class I and II allele and haplotype frequencies in 160 healthy, unrelated Albanian individuals originating from all regions of the country. The HLA genotyping was performed through a 2‐digit resolution SSOP method. The data were analysed with Arlequin and Phylip programs. No deviation was found from the Hardy–Weinberg equilibrium. A total of 17 A*, 30 B*, 12 Cw*, 13 DRB1* and 5 DQB1* alleles were identified. The six most frequent HLA‐A‐B‐DRB1 haplotypes were A*02–B*18–DRB1*11 (5.60%), A*02–B*51–DRB1*16 (4.74%), A*01–B*08–DRB1*03 (3.48%), A*24–B*35–DRB1*11 (2.77%), A*02–B*51–DRB1*13 (2.21%), A*24–B*35–DRB1*14 (1.89%). Interestingly, 12 HLA‐A‐B‐Cw‐DRB1‐DQB1 haplotypes occurred at a frequency >1%. When compared with the other populations, a close relationship was found with North Greek, Bulgarian, Macedonian, Romanian, Turkish, Cretan, Serbian, Croatian and Italian populations. A higher differentiation in allele frequency level was found with Western Europe populations. These data are the first report of HLA allele and haplotype distribution in an Albanian population inside this country. When compared with other populations, their distribution frequencies show close similarities with neighbouring populations of the entire Balkan area.     

Genetic diversity of HLA system in three populations from Zacatecas,Mexico: Zacatecas city,Fresnillo and rural Zacatecas

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 453 Mexicans from the state of Zacatecas living in Zacatecas city (N = 84), Fresnillo (N = 103) and rural communities (N = 266) to obtain information regarding allelic and haplotypic frequencies and their linkage disequilibrium. We find that the most frequent haplotypes for the state of Zacatecas include seven Native American most probable ancestry (A*02 ∼ B*39 ∼ DRB1*04 ∼ DQB1*03:02; A*02 ∼ B*35 ∼ DRB1*08 ∼ DQB1*04; A*24 ∼ B*39 ∼ DRB1*14 ∼ DQB1*03:01; A*02 ∼ B*35 ∼ DRB1*04 ∼ DQB1*03:02; A*24 ∼ B*35 ∼ DRB1*04 ∼ DQB1*03:02; A*68 ∼ B*35 ∼ DRB1*04 ∼ DQB1*03:02 and A*24 ∼ B*35 ∼ DRB1*08 ∼ DQB1*04) and two European MPA haplotypes (HLA ∼ A*01 ∼ B*08 ∼ DRB1*03:01 ∼ DQB1*02 and A*29 ∼ B*44 ∼ DRB1*07 ∼ DQB1*02). Admixture estimates revealed that the main genetic components in the state of Zacatecas are European (47.61 ± 1.85%) and Native American (44.74 ± 1.12%), while the African genetic component was less apparent (7.65 ± 1.12%). Our findings provide a starting point for the study of population immunogenetics of urban and rural populations from the state of Zacatecas and add to the growing knowledge on the population genetics of Northern Mexico.     

MHC class I and class II phenotype, gene, and haplotype frequencies in Greeks using molecular typing data

In the present study, DNA typing for HLA-A, C, B, DRB1, DRB3, DRB4, DRB5, DQA1, DQB1, and DPB1 was performed for 246 healthy, unrelated Greek volunteers of 20-59 years of age. Phenotype, genotype frequencies, Hardy-Weinberg equilibrium fit, and 3-locus haplotype frequencies for HLA-A, C, B, HLA-A, B, DRB1, HLA-DRB1, DQA1, DQB1, and HLA-DRB1, DQB1, DPB1 were calculated. Furthermore, linkage disequilibrium, deltas, relative deltas and p-values for significance of the deltas were defined. The population studied is in Hardy-Weinberg equilibrium, and many MHC haplotypes are in linkage disequilibrium. The most frequent specificities were HLA-A*02 (phenotype frequency = 44.3%) followed by HLA-A*24 (27.2%), HLA-B*51 (28.5%), HLA-B*18 (26.8%) and HLA-B*35 (26.4%) and HLA-Cw*04 (30.1%) and HLA-Cw*12 (26.8%). The most frequent MHC class II alleles were HLA-DRB1*1104 (34.1%), HLA-DQB1*0301 (54.5%) and HLA-DPB1*0401 with a phenotype frequency of 59.8%. The most prominent HLA-A, C, B haplotypes were HLA-A*24, Cw*04, B*35, and HLA-A*02, Cw*04, B*35, each of them observed in 21/246 individuals. The most frequent HLA-A, B, DRB1 haplotype was HLA-A*02, B*18, DRB1*1104 seen in 20/246 individuals, while the haplotype HLA-DRB1*1104, DQB1*0301, DPB1*0401 was found in 49/246 individuals. Finally, the haplotype DRB1*1104, DQA1*0501, DQB1*0301 was observed in 83/246 individuals. These results can be used for the estimation of the probability of finding a suitable haplotypically identical related or unrelated stem cell donor for patients of Greek ancestry. In addition, they can be used for HLA and disease association studies, genetic distance studies in the Balkan and Mediterranean area, paternity cases, and matching probability calculations for the optimal allocation of kidneys in Greece.     

Human leukocyte antigen class I and class II allele frequencies and HIV-1 infection associations in a Chinese cohort

China has one of the most rapidly spreading HIV-1 epidemics. To develop a vaccine targeted to specific human leukocyte antigen (HLA) epitopes in this population, allele distribution analysis is needed. We performed low-resolution class I and II HLA typing of a cohort of 393 subjects from mainland China using a polymerase chain reaction with sequence-specific primers (PCR-SSPs). We found 10 class I alleles present in more than 10% of the population: HLA-A*02, HLA-A*11, HLA-A*24, HLA-B*13, HLA-B*15, HLA-B*40, HLA-Cw*03, HLA-Cw*07, HLA-Cw*01, and HLA-Cw*06. Several class II alleles were found at high frequency (>or=10%): HLA-DRB3, HLA-DRB4, HLA-DRB5, HLA-DRB1*0701, HLA-DRB1*1501, HLA-DRB1*0401, HLA-DRB1*0901, HLA-DRB1*1201, HLA-DQB1*0601, HLA-DQB1*0301, HLA-DQB1*0201, HLA-DQB1*0501, and HLA-DQB*0303. We also estimated 2- and 3-locus haplotype frequencies. Because this cohort contained 280 HIV-1-seropositive and 113 HIV-1-seronegative individuals, we compared allele and haplotype frequencies between the infected and control groups to explore correlations between HLA antigens and susceptibility/resistance to HIV infection. The HLA-B*14 allele was only found in the HIV-1-seropositive group, and many 2-locus haplotypes were significantly overrepresented in this group: HLA-B*14/Cw*08, HLA-B*51/Cw*14, HLA-A*02/B*13, HLA-A*31/Cw*14, HLA-A*02/Cw*06, and the class II haplotype HLA-DRB1*1301/DQB1*0601. Alleles significantly increased in the HIV-1-seronegative controls were HLA-B*44, HLA-Cw*04, and HLA-DRB1*1402. Overrepresented 2-locus haplotypes in the control group were HLA-B*44/Cw*04, HLA-A*31/Cw*03, HLA-A*03/Cw*07, HLA-A*11/B*13, HLA-A*11/B*38, HLA-A*24/B*52, and HLA-A*11/Cw*01. The 3-locus haplotypes HLA-A*24/Cw*03/B*40 and HLA-A*02/B*15/DRB1*1201 were found to be increased significantly in the control group. These data contribute to the database of allele frequencies and associations with HIV infection in the Chinese population.     

HLA-A, -B, -DRB1 and -DQB1 polymorphisms among Iraqi Arabs

In this report, HLA polymorphisms (A, B, DRB1 and DQB1 loci) were determined in 149 unrelated Iraqi Arab potential bone marrow and kidney donors. Molecular genotyping was carried out by polymerase chain reaction followed by specific oligonucleotide probe hybridizations. Data were analyzed by Arlequin software. HLA-A, -B and -DRB1 genotype frequencies were significantly deviated from Hardy-Weinberg equilibrium, while HLA-DQB1 frequencies showed no deviation. A*03, B*35, DRB1*11 and DQB1*02 were the most frequent allele groups, while A*02-B*07-DRB1*04-DQB1*03 was the most frequent haplotype. HLA data are available in the Allele Frequencies Net Database (AFND: 3680) under the population name “Iraq Arabs”.     

A single center study of protective and susceptible HLA alleles and haplotypes with end-stage renal disease in China

Chronic kidney disease (CKD) is becoming a global public health problem and usually cause End-Stage Renal Disease (ESRD) in the end of progression. To analyze the associations of HLA-A, -B, -C, -DRB1 and -DQB1 alleles at high resolution with ESRD in Jiangsu province of China, a total of 499 unrelated patients with ESRD from the First Affiliated Hospital with Nanjing Medical University and 1584 healthy controls from Jiangsu Branch of Chinese Marrow Donor Program (CMDP) were genotyped at HLA-A, -B, -C, -DRB1 and -DQB1 loci. Statistical analysis was applied to compare the differences of HLA allele frequencies between patients with ESRD and healthy controls. As results, no protective allele at A locus was found and the susceptible alleles were A*11:01 and A*31:01. At B locus, B*15:01, B*55:02 and B*39:05 emerged as susceptible alleles, whereas no protective allele was found. At C locus, C*06:02 and C*07:01 emerged as protective alleles and no susceptible allele was found. At DRB1 locus, six alleles including DRB1*03:01, DRB1*04:03, DRB1*04:04, DRB1*04:05, DRB1*11:01 and DRB1*12:02 emerged as susceptible alleles, while DRB1*15:01 emerged as a protective allele. At DQB1 locus, DQB1*02:01, DQB1*03:01, DQB1*03:02 and DQB1*04:01 emerged as susceptible alleles, while DQB1*06:02 and DQB1*06:09 emerged as protective alleles. Haplotype A*11:01-C*03:03-B*15:01-DRB1*11:01-DQB1*03:01 containing four susceptible alleles was regarded as the most susceptible haplotype. The susceptible alleles and haplotypes might be used as some important risk classification markers. Besides, in the consanguineous renal transplantation, it would be very beneficial for the long-term survival of renal transplant patients to avoid the susceptible alleles and haplotypes in selecting optimal donors.     

Characteristics of HLA class I and class II polymorphisms in Rwandan women

OBJECTIVE: To define HLA class I and class II polymorphisms in Rwandans. METHODS: PCR-based HLA genotyping techniques were used to resolve variants of HLA-A, B, and C to their 2- or 4-digit allelic specificities, and those of DRB1 and DQB1 to their 4- or 5-digit alleles. RESULTS: Frequencies of 14 A, 8 C, and 14 B specificities and of 13 DRB1 and 8 DQB1 alleles were >/=0.02 in a group of 280 Rwandan women. These major HLA factors produced 6 haplotypes extending across the class I and class II regions: A*01-Cw*04-B* 4501-DRB1*1503-DQB1*0602 (A1-Cw4-B12- DR15 - DQ6), A * 01 - Cw * 04 - B * 4901 -DRB1 * 1302-DQB1*0604 (A1-Cw4-B21-DR13-DQ6), A*30 - Cw*04 - B*15 - DRB1*1101 - DQB1*0301 (A19-Cw4-B15-DR11-DQ7), A*68-Cw*07-B* 4901-DRB1*1302-DQB1*0604(A28-Cw7-B21- DR13 - DQ6), A*30 - Cw*07 - B*5703 - DRB1* 1303-DQB1*0301(A19 - Cw7 - B17 - DR13 - DQ7), and A*74-Cw*07-B*4901-DRB1*1302-DQB1* 0604 (A19-Cw7-B21-DR13-DQ6), respectively. Collectively, these extended haplotypes accounted for about 19% of the total. Other apparent class I-class II haplotypes (e.g., Cw*17-B*42-DRB1*0302-DQB1*0402, Cw*06- B*58-DRB1*1102-DQB1*0301, and Cw*03- B*15-DRB1*03011-DQB1*0201) did not extend to the telomeric HLA-A locus, and other 3-locus class I haplotypes (e.g., A*68-Cw*04-B*15, A*74-Cw*04-B*15, and A*23-Cw*07-B*4901) completely or partially failed to link with any specific class II alleles. DISCUSSION: Frequent recombinations appeared to occur between the three evolutionarily conserved HLA blocks carrying the class I and class II loci. The HLA class I profile seen in Rwandans was not directly comparable with those known in the literature, although the class II profile appeared to resemble those in several African populations. These data provide additional evidence for the extensive genetic diversity in Africans.     

Immunogenetics of two new HLA alleles: A*0108 and B*4031

Two new alleles, HLA-A*0108 and B*4031, were identified in north-western European Caucasoid subjects. A*0108 differed from A*010101 by a single substitution (C to T) at position 216 in exon 3, resulting in an amino acid difference of Arg to Trp at position 163. It was present on a haplotype with B*1501/60/70/71; Cw*0303; DRB1*1301; DRB3*0202; DQA1*0103; DQB1*0603 and its product reacted as a normal HLA-A1 specificity. B*4031 differed from B*4001 by two nucleotides in exon 3 (positions 20 (G to C) and 69 (A to G)) resulting in two amino acid differences (Arg to Ser at position 97 and Asn to Asp at position 114). It was found on a haplotype with HLA-A*03; Cw*0304; DRB1*0404/32; DRB4*0101/3/5; DQA1*03; DQB1*0302 and has the HLA-B60 specificity. Both alleles have frequencies of < 0.0002 in the largely north-western European Caucasoid blood donor population resident in Wales.     

The contribution of HLA class I and II alleles and haplotypes to the investigation of the evolutionary history of Tunisians

The frequencies of HLA class I and class II alleles and haplotypes of 104 healthy unrelated Tunisians were analyzed by high-resolution PCR-reverse dot blot hybridization, and was compared with other Mediterranean and Sub-Saharan Africans using genetic distances measurements, Neighbor-joining dendrograms, correspondence, and extended haplotypes analysis. The most frequent HLA class I A alleles were A*02, A*24, and A*30, while the most frequent B alleles were B*44, followed by B*50, B*51, and B*07. Among HLA class II DRB alleles analyzed, the most frequent were DRB1*0301, DRB1*0701, DRB1*1501, followed by DRB1*1303 and DRB1*0102; for DQB1, they were DQB1*0301 and DQB1*0201. Three-locus haplotype analysis revealed that A*03-B*07-DRB1*1503 and A*02-B*44-DRB1*0402 were the most common HLA class I and II haplotypes in this population. Compared with other communities, our result indicate that Tunisians are very related to North Africans and Western Europeans, particularly Iberians, and that Tunisians, Algerians, and Moroccans are close to Berbers suggesting little genetic contribution of Arabs who populated the area in 7th to 8th century AD. The similarities and differences between Tunisians and neighboring and related communities in HLA genotype distribution provide basic information for further studies of the MHC heterogeneity among Mediterranean and North African countries, and as reference for further anthropological studies.     

Human leukocyte antigen class II allele frequencies and haplotype association in Iranian normal population.

The polymorphism of the HLA class II genes DRB1, DQA1, and DQB1 was investigated in 100 unrelated Iranian individuals from Fars province in Southern Iran, using the restriction fragment length polymorphism (RFLP) method. Subtyping of DRB1*04, *15, and *16 alleles was performed using PCR amplification with sequence specific primes (PCR-SSP). The allele and the haplotype frequencies were calculated. The most common DRB1 alleles were DRB1*11, DRB1*15, and DRB1*04 with a frequency of 25.0%, 14.5%, and 10.5%, respectively. In contrast, the allelic frequency of DRB1*12 and DRB1*08 was very low (1.5% for each). In the DR15 group DRB1*1501 was the most prevalent variant (6.0%). Concerning DR4, the most common alleles were DRB1*0405 and DRB1*0402 (3.5% for each). Interestingly, DRB1*0402 was associated with DQB1*0302 and DRB1*0405 was associated with DQB1*0302 and DQB1*02, the latter being a rare DRB1/DQB1 haplotype in Caucasian individuals. The most frequent DQB1 alleles were DQB1*0301 (31.0%), and DQB1*05 (22.0%). The most frequent DQA1 variants were DQA1*0501 (39.0%) and DQA1*0102 (14.5%). The most common haplotype was DRB1*11-DQB1*0301-DQA1*0501 (25.0%) followed by DRB1*0301-DQB1*02-DQA1*0501 (10%) and DRB1*0701- DQB1*02-DQA1*0201 (6.5%). Data presented in this study suggest that the Iranian population shares some HLA components with populations resident in eastern and southern European countries.     

Allele and haplotype frequencies of HLA‐A,B, C,DRB1 and DQB1 genes in polytransfused patients in ethnically diverse populations from Brazil

The red blood transfusion is a practice often used in patients with haematological and oncological diseases. However, the investigation of human leucocyte antigen (HLA) system frequency in these individuals is of great importance because multiple transfusions may lead to HLA alloimmunization. Brazil is a country that was colonized by many other ethnicities, leading to a mixed ethnicity and regionalized population. In view of the importance of HLA typing in these patients, the aim of this study was to investigate the allele and haplotype frequencies from polytransfused patients from three different regions from Brazil. HLA‐A, HLA‐B, HLA‐C, HLA‐DRB1 and HLA‐DQB1 genotyping of 366 patients was performed by PCR‐SSO, based on the Luminex technology (One Lambda^®), and the anti‐HLA class I and class II antibodies were analysed using LabScreen Single Antigen Antibody Detection (One Lambda, Inc.). Allele and haplotype frequencies of polytransfused patients of three regions from Brazil were obtained using the Arlequin program. The most frequent allele frequencies observed were HLA‐A*02, A*03, B*15, B*35, B*51, C*07, C*04, C*03, DRB1*13, DRB1*11, DRB1*07, DRB1*03, DRB1*01, DQB1*03, DQB1*02, DQB1*06 and DQB1*05. There were differences between the groups for allele variants HLA‐B*57 (between Group 1 and Group 2) and HLA‐C*12 (between Group 1 and Group 3). The most frequent haplotypes found in the sample were HLA‐A*01B*08DRB1*03, DRBI*07DQB1*02, DRB1*01DQB1*05, DRB1*13DQB1*06 and A*02B*35. HLA class I and II antibodies were detected in 77.9% and 63.9% patients, respectively, while the both alloantibodies were detected in 62 (50.9%) patients. In conclusion, the HLA typing for polytransfused patients in each region has a great importance, as seen in this study; individuals from different regions from Brazil have HLA distribution not completely homogeneous.     

High-resolution HLA allele and haplotype frequencies of the Saudi Arabian population based on 45,457 individuals and corresponding stem cell donor matching probabilities

We estimated HLA allele and haplotype frequencies of the Saudi Arabian population from a sample of 45,457 registered stem cell donors. The most frequent HLA alleles were A*02:01g (18.5%), C*06:02g (16.1%), B*51:01g (14.1%), DRB1*07:01g (16.2%), DQB1*02:01g (30.5%), and DPB1*04:01g (33.6%). The most frequent 5-locus haplotypes were A*02:05g~C*06:02g~B*50:01g~DRB1*07:01g~DQB1*02:01g (1.73%), A*02:01g~C*06:02g~B*50:01g~DRB1*07:01g~DQB1*02:01g (1.66%), and A*26:01g~C*07:02g~B*08:01g~DRB1*03:01g~DQB1*02:01g (1.38%). Furthermore, we used the calculated haplotype frequencies to estimate stem cell donor matching probabilities for Saudi Arabian donor and patient populations under various matching requirements. These results are relevant for strategic donor registry planning in the Kingdom of Saudi Arabia.     

中国汉族人群供-受者HLA-A、B、Cw、DRB1和DQB1高分辨等位基因频率分布及错配比例的研究

目的 从基因高分辨水平,分析中国汉族人群供-受者人类白细胞抗原(human leukocyte antigens,HLA)-A、B、Cw、DRB1、DQB1各位点等位基因频率和分布的多态性;及供-受者等位基因匹配情况.方法 采用基因测序分型(sequence based typing,SBT)、序列特异性寡核苷酸探针法(sequence specific oligonueleotide probe,SSOP)和序列特异性引物法(sequence specific primer,SSP),对2540名中国汉族人的(其中1168名受者,1372名供者)DNA标本进行HLA高分辨基因分型,并作统计学处理.结果 2540份样本中共检测到44种HLA-A等位基因,频率高于0.05的A*1101、A*2402、A*0201、A*0207、A*3303、A*0206、A*3001共占80.4%;81种HLA-B等位基因,频率高于0.05的B*4001、B*4601、B*5801、B*1302、B*5101共占43.0%;44种HLA-Cw等位基因,频率高于0.05的Cw*0702、Cw*0102、Cw*0304、Cw*0801、Cw*0602、Cw*0303、Cw*0302、Cw*0401共占80.3%;61种HLA-DRB1等位基因,频率高于0.05的DRB1*0901、DRB1*1501、DRB1*1202、DRB1*0803、DRB1*0701、DRB1*0405、DRB1*0301、DRB1*1101共占70.1%;22种HLA-DQB1等位基因,频率高于0.05的DQB1*0301、DQB1*0303、DQB1*0601、DQB1*0602、DQB1*0202、DQB1*0302、DQB1*0401、DQB1*0502、DQB1*0201共占87.4%.这5个位点均处于杂合子缺失状态,其中A、B、DRB1位点符合HardyWeinberg平衡(Hardy-Weinberg equi1ibrium,HWE)(P＞0.05);Cw、DQB1位点偏离HWE(P＜0.05);排除个别基因型观察值与期望值偏差较大外,这5个位点均符合HWE.在供-受者数据的比较中,HLA全相合(10/10)的比例仅22.4%;单个等位基因错配(9/10)的比例为24.6%;两个等位基因错配(8/10)的比例为26.3%.结论 中国汉族人群高分辨水平HLA-A、B、Cw、DRB1,DQB1等位基因频率及分布特点,对非亲缘造血干细胞移植供者检索有重要参考价值;并为中华骨髓库数据入库和利用提供遗传学依据.

Abstract：

Objective To analyze the allele frequencies and polymorphism of human leukocyte antigens (HLA) -A, B, Cw, DRB1 and DQB1 between donors-recipients on high-resolution typing; and to analyze the matching and mismatching proportion between donors and recipients. Methods HLA highresolution types were determined by sequence based typing (SBT), sequence specific oligonucleotide probe (SSOP) and sequence specific primer (SSP) on 2540 unrelated Chinese Han individuals including 1168 recipients and 1372 donors, then statistical analyses were carried out. Results Forty-four HLA-A alleles were detected, and among them the frequencies of A * 1101, A * 2402, A * 0201, A * 0207, A * 3303, A *0206 and A * 3001 exceeded 0.05, and accounted for 80.4%. Eighty-one HLA-B alleles were detected, and frequencies of B * 4001, B * 4601, B * 5801, B * 1302 and B * 5101 exceeded 0. 05, and accounted for 43. 0% of total. There were 44 HLA- Cw alleles, among them the frequencies of Cw * 0702, Cw * 0102,Cw * 0304, Cw * 0801, Cw * 0602, Cw * 0303, Cw * 0302 and Cw * 0401 exceeded 0.05, and were 80.3 %of total. There were 61 HLA-DRB1 alleles, the frequencies of DRB1 * 0901, DRB1 * 1501, DRB1 * 1202,DRB1 * 0803, DRB1 * 0701, DRB1 * 0405, DRB1 * 0301 and DRB1 * 1101 exceeded 0. 05, and were 70. 1% of total. Finally, 22 HLA-DQB1 alleles were detected, the frequencies of DQB1 * 0301, DQB1 *0303, DQB1 * 0601, DQB1 * 0602, DQB1 * 0202, DQB1 * 0302, DQB1 * 0401, DQB1 * 0502 and DQB1 *0201 exceeded 0. 05, and they were 87.4% of total. All the five loci were of heterozygote deficiency. The HLA-A, B and DRB1 loci conformed to Hardy-Weinberg equilibrium (HWE) (P＞0. 05); but HLA-Cw and HLA-DQB1 loci did not (P＜0.05). Except several particular genotypes, all the five loci conformed to HWE. After comparing data between donors and recipients, only 22.4% of recipients found HLA matched donors (10/10); 24. 6% of recipients found single HLA allele mismatched donors (9/10); 26. 3% of recipients had two HLA alleles mismatched donors (8/10). Conclusion The characteristics of allele frequencies and polymorphism of HLA-A, B, Cw, DRB1 and DQB1 on high-resolution typing in Chinese Han population is valuable for donor searching in unrelated hematopoietic stem cell transplantation, and it provides genetic basis for donor registry and usage of donor resource for Chinese Marrow Donor Program.     

HLA class II susceptibility pattern for type 1 diabetes (T1D) in an Iranian population

This study aimed to determine the HLA‐DRB1/HLA‐DQB1 susceptibility and protection pattern for type 1 diabetes (T1D) in a population from Hamadan, north‐west of Iran. A total of 133 patients with T1D were tested for HLA‐DRB1 and HLA‐DQB1 alleles using PCR‐SSP compared to 100 ethnic‐matched healthy controls. Alleles and haplotypes frequencies were compared between both groups. The most susceptible alleles for disease were HLA‐DRB1*03:01, DRB1*04:02, DQB1*02:01 and DQB1*03:02, and protective alleles were HLA‐DRB1*07:01, *11:01, *13:01, *14:01 and DRB1*15 and HLA‐DQB1*06:01, *06:02 and *06:03. Haplotype analysis revealed that patients with T1D had higher frequencies of DRB1*03:01–DQB1*02:01 (OR = 4.86, P < 10^?7) and DRB1*04:02–DQB1*03:02 (OR = 9.93, P < 10^?7) and lower frequencies of DRB1*07:01–DQB1*02:01 (P = 0.0005), DRB1*11:01–DQB1*03:01 (P = 0.001), DRB1*13:01–DQB1*06:03 (P = 0.002) and DRB1*15–DQB1*06:01 (P = 0.001) haplotypes compared to healthy controls. Heterozygote combination of both susceptible haplotypes (DR3/DR4) confers the highest risk for T1D (RR = 18.80, P = 4 × 10^?5). Additionally, patients with homozygote diplotype, DR3/DR3 and DR4/DR4, showed a similar risk with less extent to heterozygote combination (P = 0.0004 and P = 0.01, respectively). Our findings not only confirm earlier reports from Iranians but also are in line with Caucasians and partly with Asians and some African patients with T1D. Remarkable differences were the identification of DRB1*04:01–DQB1*03:02, DRB1*07:01–DQB1*03:03 and DRB1*16–DQB1*05:02 as neutral and DRB1*13:01–DQB1*06:03 as the most protective haplotypes in this study.     

Polymorphism of HLA class I genes in the Brazilian population from the Northeastern State of Pernambuco corroborates anthropological evidence of its origin

The allelic distribution of human leukocyte antigen (HLA) class I genes (HLA-A, HLA-B, and HLA-Cw) of the population from the State of Pernambuco in Northeastern Brazil was studied in a sample of 101 healthy unrelated individuals. Low to medium resolution HLA class I typing was performed using polymerase chain reaction-amplified DNA hybridized to sequence specific primers (PCR-SSPs). Twenty allele groups were detected for HLA-A, 28 for HLA-B, and 14 for HLA-Cw. The most frequent alleles were HLA-A*02(0.2871), HLA-B*15(0.1238), and HLA-Cw*04(0.2277), and the most frequent genotypes were A*02/A*02(0.0990), B*15/B*15(0.0594), and Cw*04/Cw*04 and Cw*07/Cw*07, both with a frequency of 0.0792. The observed heterozygosity for the studied loci was 79.21% for HLA-A, 87.13% for HLA-B, and 77.23% for HLA-Cw. The most frequent haplotype was A*02-Cw*04-B*35(0.0485), which is also present in Western European, Amerindian, and Brazilian Mulatto populations, but absent in African populations. Taken together, these data corroborate the historic anthropological evidences of the origin of the Northeastern Brazilian population from Pernambuco.