HLA Genes in Mayos Population from Northeast Mexico

HLA class I and class II alleles have been studied in 60 unrelated people belonging to Mayos ethnic group, which lives in the Mexican Pacific Sinaloa State. Mayos HLA profile was compared to other Amerindians and worldwide populations’ profile. A total of 14,896 chromosomes were used for comparisons. Genetic distances between populations, Neigbour-Joining dendrograms and correspondence analyses were performed to determine the genetic relationship among population. The new specific Mayo HLA haplotypes found are: HLA-A*02-B*35-DRB1*1406-DQB1*0301; HLA-A*02-B*48-DRB1*0404-DQB1*0302; HLA-A*24-B*51-DRB1*0407-DQB1*0302 and HLA-A*02-B*08-DRB1*0407-DQB1*0302. However, the typical Meso American HLADRB1*0407 represents a 40% of all DRB1 alleles. While common HLA characteristics are found in Amerindian distant ethnic groups, still new group specific HLA haplotypes are being found, suggesting that a common founder effect (i.e. high DRB1*0407) is noticed. Moreover, new HLA haplotypes are almost certainly appearing along time probably due to specific pathogen (?) selection for diversity. Mayo language is close to the Tarahumara one (another geographically close group); notwithstanding both groups are not genetically close according to our results, showing again the different evolution of genes and languages, which do not correlate. Finally, Sinaloa is one of the Mexican States in which more European genes are found. However, the results presented in this paper, where no European HLA genes are seen in Mayos, should have a bearing in establishing transplant programs and in HLA and disease studies.Key Words: Amerindians, HLA, mayos, mexica, nahua, transplant.     

The polymorphisms of HLA class Ⅰ and Ⅱalleles were not associated with severe acute respiratory syndrome among recovered patients in Beijing: a case-control study

Severe acute respiratory syndrome (SARS) is a viral respiratory illness caused by a novel coronavirus (SARS-CoV), which emerged as a pandemic in 2003. The mechanism of the immune reaction initiated by SARS-CoV still remains unclear. Here we aimed to describe the genetic patterns of high-resolution HLA-A, -B, -C, -DRB1, and -DQB1, loci in recovered SARS patients from Beijing and examine the association between HLA genes and susceptibility or resistance to SARS. A total of 70 recovered Chinese Han SARS patients were recruited to donate convalescent plasma in 2003. HLA high-resolution typing was carried out using sequence based typing (SBT). Allele frequencies were calculated by direct counting, and were compared with the frequencies of HLA alleles of donors recruited by the China Marrow Donor Program between 2002 and 2015 using Fisher''s exact test. Significance of association was defined according to the Bonferroni method for multiple comparisons. We observed 20, 35, 21, 25, and 17 alleles respectively at HLA-A, -B, -C, -DRB1, and -DQB1 loci among the 70 recovered patients. We identified 12 alleles (HLA-A*02:10, -A*02:93, -A*03:02, -B*08:01, -B*15:152, -B*37:01, -DRB1*10:01, -DRB1*11:03, -DRB1*14:10, -DRB1*14:12, -DRB1*15:02, and -DQB1*05:10) showing a nominal association with SARS (P<0.05), but none remained significant after Bonferroni correction. The study suggests that high-resolution HLA alleles are unlikely to contribute significantly to the susceptibility or resistance to SARS-CoV infection in the northern Chinese population.     

HLA Class I and Class II Associations with ESRD in Saudi Arabian Population

Background

Chronic renal failure (CRF) leads in the majority of instances to end stage renal disease (ESRD) requiring renal replacement therapy. Our interest was to evaluate the possible associations of HLA class I and class II antigens with ESRD independent of other factors, in Saudi Arabia population.

Methodology

A retrospective study to determine the HLA class I and class II polymorphisms and their association with ESRD, was performed on 350 patients with ESRD, and 105 healthy unrelated control. Patients and control groups were typed by SSOP lumenix techniques. The alleles positively associated to the ESRD were: HLA-B*15, B*18, B*49 - DRB1*03, negatively associated alleles were A*26, HLA-B*39, B*50. The haplotypes positively associated with ESRD were: HLA-A*01-DRB1*13 and HLA-A*30-DRBI*03. The negatively associated haplotypes were: HLA-A*02-B*39, A*02-B*50, A*24-B*35, A*24-B*58, A*24-DRB1*16, A*68-DRB1*04, A*02-DQB1*03, A*29-DQB1*02, A*29-DOB1*05 and B*27-DRB1*07 and the last one is the most significant protective haplotypes.

Conclusion

The high Relative Risk (RR) observed and its statistical correlation reflect the strength of the described association between HLA antigens and ESRD.     

The polymorphisms of HLA class Ⅰ and Ⅱalleles were not associated with severe acute respiratory syndrome among recovered patients in Beijing: a case-control study

Severe acute respiratory syndrome (SARS) is a viral respiratory illness caused by a novel coronavirus (SARS-CoV), which emerged as a pandemic in 2003. The mechanism of the immune reaction initiated by SARS-CoV still remains unclear. Here we aimed to describe the genetic patterns of high-resolution HLA-A, -B, -C, -DRB1, and -DQB1, loci in recovered SARS patients from Beijing and examine the association between HLA genes and susceptibility or resistance to SARS. A total of 70 recovered Chinese Han SARS patients were recruited to donate convalescent plasma in 2003. HLA high-resolution typing was carried out using sequence based typing (SBT). Allele frequencies were calculated by direct counting, and were compared with the frequencies of HLA alleles of donors recruited by the China Marrow Donor Program between 2002 and 2015 using Fisher's exact test. Significance of association was defined according to the Bonferroni method for multiple comparisons. We observed 20, 35, 21, 25, and 17 alleles respectively at HLA-A, -B, -C, -DRB1, and -DQB1 loci among the 70 recovered patients. We identified 12 alleles (HLA-A*02:10, -A*02:93, -A*03:02, -B*08:01, -B*15:152, -B*37:01, -DRB1*10:01, -DRB1*11:03, -DRB1*14:10, -DRB1*14:12, -DRB1*15:02, and -DQB1*05:10) showing a nominal association with SARS (P<0.05), but none remained significant after Bonferroni correction. The study suggests that high-resolution HLA alleles are unlikely to contribute significantly to the susceptibility or resistance to SARS-CoV infection in the northern Chinese population.     

HLA class II polymorphism in autochthonous population of Gorski kotar, Croatia

The aim of this study was to examine frequencies and haplotypic associations of HLA class II alleles in autochthonous population of Gorski kotar (Croatia). HLA-DRB1, -DQA1 and -DQB1 alleles were determined by DNA based PCR typing in 63 unrelated inhabitants from Gorski kotar whose parents and ancestors were born and lived in tested area for at least over four generations. A total of 13 HLA-DRB1, 12 DQA1 and 14 DQB1 alleles were identified. The most frequent HLA class II genes in Gorski kotar population are: HLA-DRB1*13 (af = 0.150), -DRB1*03 (af = 0.142), -DRB1*07 (af = 0.119), and -DRB1*11 (af = 0.119), HLA-DQA1*0501 (af = 0.278), -DQA1*0102 (af = 0.183), -DQA1*0201 (af = 0.127) and HLA-DQB1*0301 (af = 0.157), -DQB1*0201 (af = 0.139), -DQB1*0501 (af = 0.111). We have identified 24 HLA class II three-locus haplotypes. The most common haplotypes in Gorski kotar population are DRB1*03-DQA* 0501-DQB1*0201 (0.120), DRB1*11-DQA1*0501-DQB1*0301 (0.111) and DRB1*07-DQA1*0201-DQB1*0202 (0.094). The allelic frequencies and populations distance dendrogram revealed the closest relationships of Gorski kotar population with Slovenians, Germans, Hungarians and general Croatian population, which is the result of turbulent migrations within this microregion during history.     

内蒙古地区蒙古族HLA-A、B、DRB1基因座多态性分析

应用序列特异性寡核苷酸探针反向斑点杂交技术对内蒙古地区蒙古族106名无关健康个体的HLA-A、B和DRB1 基因座进行基因分型, 以研究内蒙古地区蒙古族人群HLA-A、B、DRB1基因座的等位基因及其组成的单倍型频率分布特征。 采用最大数学预期值算法计算HLA基因座的等位基因频率和单倍型频率。106 名内蒙古地区蒙古族个体的HLA-A、B、DRB1基因座分别检出13、29、13个等位基因。高频单倍型分别为 HLA-A*02-B*46 (0.0510); HLA-A*02-B*13(0.0495); HLA-A*02-B*51(0.0442); HLA-B*13-DRB1*07 (0.0555); HLA- B*46-DRB1*09(0.0378); HLA-B*35-DRB1*13(0.03300); HLA-A*02-B*13-DRB1*07(0.033019); HLA-A*02-B*46- DRB1*09(0.031985)。研究表明: 内蒙古地区蒙古族人群HLA基因座的等位基因和单倍型具有较高的遗传多态性。HLA- A*24-B*14, HLA-A*32-B*63在该民族具有极强的连锁不平衡。     

HLA Class I and Class II Alleles and Haplotypes Confirm the Berber Origin of the Present Day Tunisian Population

In view of its distinct geographical location and relatively small area, Tunisia witnessed the presence of many civilizations and ethnic groups throughout history, thereby questioning the origin of present-day Tunisian population. We investigated HLA class I and class II gene profiles in Tunisians, and compared this profile with those of Mediterranean and Sub-Sahara African populations. A total of 376 unrelated Tunisian individuals of both genders were genotyped for HLA class I (A, B) and class II (DRB1, DQB1), using reverse dot-blot hybridization (PCR-SSO) method. Statistical analysis was performed using Arlequin software. Phylogenetic trees were constructed by DISPAN software, and correspondence analysis was carried out by VISTA software. One hundred fifty-three HLA alleles were identified in the studied sample, which comprised 41, 50, 40 and 22 alleles at HLA-A,-B,-DRB1 and -DQB1 loci, respectively. The most frequent alleles were HLA-A*02:01 (16.76%), HLA-B*44:02/03 (17.82%), HLA-DRB1*07:01 (19.02%), and HLA-DQB1*03:01 (17.95%). Four-locus haplotype analysis identified HLA-A*02:01-B*50:01-DRB1*07:01-DQB1*02:02 (2.2%) as the common haplotype in Tunisians. Compared to other nearby populations, Tunisians appear to be genetically related to Western Mediterranean population, in particular North Africans and Berbers. In conclusion, HLA genotype results indicate that Tunisians are related to present-day North Africans, Berbers and to Iberians, but not to Eastern Arabs (Palestinians, Jordanians and Lebanese). This suggests that the genetic contribution of Arab invasion of 7^th-11^th century A.D. had little impact of the North African gene pool.     

Genetic history of Aleuts of the Komandor islands from results of analyzing variability of class II HLA genes

Variability of the HLA class II genes (alleles of the DRB1, DQA1, and DQB1 loci) was investigated in a sample of Aleuts of the Commanders (n = 31), whose ancestors inhabited the Commander Islands for many thousand years. Among 19 haplotypes revealed in Aleuts of the Commanders, at most eight were inherited from the native inhabitants of the Commander Islands. Five of these haplotypes (DRB1*0401-DQA1*0301-DQB1*0301, DRB1*1401-DQA1*0101-DQB1*0503, DRB1*0802-DQA1*0401-DQB1*0402, DRB1*1101-DQA1*0501-DQB1*0301, and DRB1*1201-DQA1*0501-DQB1*0301) were typical of Beringian Mongoloids, i.e., Coastal Chukchi and Koryaks, as well as Siberian and Alaskan Eskimos. Genetic contribution of the immigrants to the genetic pool of proper Aleuts constituted about 52%. Phylogenetic analysis based on Transberingian distribution of the DRB1 allele frequencies favored the hypothesis on the common origin of Paleo-Aleuts, Paleo-Eskimos, and the Indians from the northwestern North America, whose direct ancestors survived in Beringian/southwestern Alaskan coastal refugia during the late Ice Age.     

Genetic History of Aleuts of the Commander Islands as Revealed by the Analysis of the HLA Class II Gene Variability

Variability of the HLA class II genes (alleles of the DRB1, DQA1, and DQB1 loci) was investigated in a sample of Aleuts of the Commanders (n = 31), whose ancestors inhabited the Commander Islands for many thousand years. Among 19 haplotypes revealed in the Aleuts of the Commanders, at most eight were inherited from the native inhabitants of the Commander Islands. Five of these haplotypes (DRB1*0401-DQA1*0301-DQB1*0301, DRB1*1401-DQA1*0101-DQB1*0503, DRB1*0802-DQA1*0401-DQB1*0402, DRB1*1101-DQA1*0501-DQB1*0301, and DRB1*1201-DQA1*0501-DQB1*0301) were typical of Beringian Mongoloids, i.e., Coastal Chukchi and Koryaks, as well as Siberian and Alaskan Eskimos. Genetic contribution of the immigrants to the genetic pool of the proper Aleuts constituted about 52%. Phylogenetic analysis based on Transberingian distribution of the DRB1 allele frequencies favored the hypothesis on the common origin of the Paleo-Aleuts, Paleo-Eskimos, and the Indians from the northwestern North America, whose direct ancestors survived in Beringian/southwestern Alaskan coastal refugia during the late Ice Age.     

Allele polymorphism and haplotype diversity of HLA-A, -B and -DRB1 loci in sequence-based typing for Chinese Uyghur ethnic group

HLA haplotype analysis has important application value in human population genetics, anthropological research and HLA matching transplantation. Based on HLA-A, -B, -C, -DRB1 and -DQB1 genotyping data from 663 families including 663 leukemia patients and 991 related donors, the allele frequency (AF) and haplotype frequency (HF) of two-, three- and five-locus haplotype distribution patterns in the Chinese Han population were determined by family segregation. A total of 38 alleles at A locus, 75 alleles at B locus, 35 alleles at C locus, 53 alleles at DRB1 locus and 22 alleles at DQB1 locus were discovered in this population. The frequencies of these alleles were basically consistent with those of previous reports except for some tiny differences. The study found 11 A-C, 15 C-B, 4 B-DRB1 and 11 DRB1-DQB1 two-locus haplotypes with a frequency over 2%. The number of A-C-B and A-B-DRB1 three-locus haplotype with a frequency over 1% were 11 and 3 respectively. The most common HLA-A-C-B-DRB1-DQB1 haplotype (HF>1%) were A*3001-C*0602-B*1302-DR*0701-DQ*0202 (4.30%), A*0207-C*0102-B*4601-DR*0901-DQ*0303 (3.07%), A*3303-C*0302-B*5801-DR*0301-DQ*0201 (1.49%) and A*1101-C*0102-B*4601-DR*0901-DQ*0303 (1.01%). The results are helpful for finding matching donors for hematopoietic stem cell transplant patients and also contribute to transplant immunology, HLA-related diseases, research of human genetics and other fields.     

An Analysis of HLA-A, -B,and -DRB1 Allele and Haplotype Frequencies of 21,918 Residents Living in Liaoning,China

HLA-A, -B and -DRB1 allele frequencies and their haplotype frequencies in 21,918 Chinese residents living in Liaoning Province, who were registered as volunteer donors of China Marrow Donor Registry, were investigated. They are composed of 93.37% Han Chinese, 5.1% Manchus, 0.57% Mongols, 0.46% Hui persons, 0.29% Koreans and 0.14% Xibe ethnic group. In total eighteen different HLA-A alleles, forty-eight different HLA-B alleles and fourteen different HLA-DRB1 alleles have been identified. Their frequencies are in agreement with the Hardy-Weinberg equilibrium. For Han Chinese in Liaoning, 1,534 different HLA-A-B-DRB1 haplotypes were identified, with a frequency of higher than 0.01%. A*30-B*13-DRB1*07, A*02-B*46-DRB1*09 and A*02-B*13-DRB1*12 are the most frequent haplotypes among Liaoning Han. While Liaoning Han, Liaoning Manchu, Liaoning Mongol, Liaoning Hui and Liaoning Korean share the northern Han characteristic haplotypes, all minority ethnic groups with the exception of Liaoning Manchu have developed their own unique HLA profiles. This dataset characterizes the HLA allele and haplotype frequencies in the Liaoning area and suggests that it is different from those in other parts of China and ethnic groups, which implicates transplant donor searching strategies and studies on population genetics.     

Allele and haplotype frequencies of human leukocyte antigen-A, -B, -C,-DRB1, and -DQB1 in Chinese patients with hematological diseases

The human leukocyte antigen (HLA) system plays a central role in the immune response to pathogens, as well as in organ and allogenic hematopoietic stem cell transplantation (HSCT). Finding a five-locus (i.e., HLA-A, -B, -C, -DRB1, and -DQB1) matched unrelated donor for a patient awaiting HSCT is a major clinical challenge, due to the lack of HLA-identical sibling donors and the high polymorphism of HLA. To date, most studies providing HLA allele frequencies (AF) and haplotype frequencies (HF) in Chinese populations have focused on donors instead of the recipients and have provided data for three loci (HLA-A, -B, and -DR); however, data from five-locus HLA typing in a large sample of patients, especially those with hematological diseases, remains unavailable. Therefore, this study was designed to determine HLA AF and two-, three-, four- and five-locus HF in a large cohort of Chinese Han patients with hematological diseases. The AF and the HF were determined using high-resolution HLA typing data from 2,878 patients. The total number of HLA-A, -B, -C, -DRB1, and -DQB1 alleles was determined to be 48, 92, 49, 52, and 24, respectively. Hardy-Weinberg equilibrium (HWE) analyses indicated significant deviations from HWE for HLA-A, -C, -DRB1, and -DQB1 AF, but not for HLA-B locus. The three most common alleles at each locus were A*11:01, A*24:02, A*02:01; B*46:01, B*40:01, B*13:02; C*01:02, C*07:02, C*06:02; DRB1*09:01, DRB1*15:01, DRB1*07:01; DQB1*03:01, DQB1*03:03, and DQB1*06:01. Our data may help to determine whether the current bone marrow registry contains sufficient diversity to meet the demand.     

Susceptibility alleles and haplotypes of human leukocyte antigen DRB1, DQA1, and DQB1 in autoimmune polyglandular syndrome type III in Japanese population

BACKGROUND: It has been reported that HLA class II haplotypes DRB1*0405-DQA1*0303-DQB1*0401 and DRB1*0901-DQA1*0302-DQB1*0303 are major susceptibility haplotypes for type 1 diabetes mellitus (DM) in Japanese population. However, little has been reported on the susceptibility HLA class II haplotypes in Japanese patients with autoimmune polyglandular syndrome type II and type III (APS III). PATIENTS AND METHODS: HLA class II haplotypes of DRB1-DQA1-DQB1 in 31 patients with APS III, 14 patients with Hashimoto's thyroiditis alone, and 15 patients with Graves' disease alone were examined in Japanese population. APS III patients were divided into three groups (A, B, and C) depending on the combination of autoimmune endocrine diseases. RESULTS: In 13 APS III patients with both Hashimoto's thyroiditis and type 1 DM (group A), the haplotype frequencies of the HLA DRB1*0802-DQA1*0401-DQB1*0402 and DRB1*0901-DQA1*0302-DQB1*0303 were significantly higher than in the controls. In patients with Hashimoto's thyroiditis alone, the haplotype frequency of DRB1*0901-DQA1*0302-DQB1*0303 was significantly higher than in controls, whereas the frequency of DRB1*0802-DQA1*0401-DQB1*0402 did not differ significantly from those in the controls. In 11 APS III patients with both Graves' disease and type 1 DM (group B), the haplotype frequencies of HLA DRB1*0405-DQA1*0303-DQB1*0401 and DRB1*0802-DQA1*0301-DQB1*0302 were significantly higher than in controls. In patients with Graves' disease alone, the haplotype frequency of DRB1*0803-DQA1*0103-DQB1*0601 were significantly higher than those in controls, suggesting that the susceptibility haplotypes for group B APS III differed from those for Graves' disease alone. In 7 APS III patients with both autoimmune thyroid diseases and pituitary disorders (group C), the haplotype frequency of HLA DRB1*0405-DQA1*0303-DQB1*0401 was significantly higher than in controls. CONCLUSIONS: Susceptible HLA class II haplotypes of DRB1-DQA1-DQB1 for APS III differ between the Japanese and Caucasian populations. More interestingly, the susceptible HLA class II haplotypes differ among the three types of Japanese APS III and are not merely a combination of susceptibility haplotypes of each endocrine disease.     

Distribution of HLA class Ⅰ and class Ⅱ haplotypes in Chinese Han population based on family segregation

HLA haplotype analysis has important application value in human population genetics, anthropological research and HLA matching transplantation. Based on HLA-A, -B, -C, -DRB1 and -DQB1 genotyping data from 663 families including 663 leukemia patients and 991 related donors, the allele frequency (AF) and haplotype frequency (HF) of two-, three- and five-locus haplotype distribution patterns in the Chinese Han population were determined by family segregation. A total of 38 alleles at A locus, 75 alleles at B locus, 35 alleles at C locus, 53 alleles at DRB1 locus and 22 alleles at DQB1 locus were discovered in this population. The frequencies of these alleles were basically consistent with those of previous reports except for some tiny differences. The study found 11 A-C, 15 C-B, 4 B-DRB1 and 11 DRB1-DQB1 two-locus haplotypes with a frequency over 2%. The number of A-C-B and A-B-DRB1 three-locus haplotype with a frequency over 1% were 11 and 3 respectively. The most common HLA-A-C-B-DRB1-DQB1 haplotype (HF>1%) were A*3001-C*0602-B*1302-DR*0701-DQ*0202 (4.30%), A*0207-C*0102-B*4601-DR*0901-DQ*0303 (3.07%), A*3303-C*0302-B*5801-DR*0301-DQ*0201 (1.49%) and A*1101-C*0102-B*4601-DR*0901-DQ*0303 (1.01%). The results are helpful for finding matching donors for hematopoietic stem cell transplant patients and also contribute to transplant immunology, HLA-related diseases, research of human genetics and other fields.     

Polymorphism of Leukocyte and Erythrocyte Antigens in Chronic Kidney Disease Patients in Southern Brazil

We investigated the polymorphism of human leukocyte antigens (HLA) and Duffy erythrocyte antigens in chronic kidney disease (CKD) patients in southern Brazil. One hundred and eighty-three CKD patients, over 18 years old, on hemodialysis, were included. HLA-A, -B and -DRB1 typing was performed using the LABType®SSO (One Lambda, Inc.). Duffy phenotypes were determined by gel column agglutination using anti-Fy^a and anti-Fy^b monoclonal anti-sera. The patients'' predominant ages ranged between 51 and 70 years (43%) and the predominant gender, ethnic group and dialysis period were, respectively, male (62%), white (62%) and 1–3 years (40%). The highest and lowest frequencies of Duffy phenotypes were Fy(a+b+) and Fy(a−b−), respectively. Nineteen HLA-A, 30 HLA-B and 13 HLA-DRB1 allele groups were identified. The most frequent HLA allele groups were HLA-A*01, -A*02, -A*03, -A*11, -A*24; HLA-B*07, -B*15, -B*35, -B*44, -B*51; HLA-DRB1*03, -DRB1*04, -DRB1*07, -DRB1*11 and -DRB1*13. Statistically significant differences were observed in the Duffy and HLA polymorphisms compared between CKD patients and healthy subjects. The Fy(a+b−) phenotype (p<0.0001, OR = 2.56, 95% CI = 1.60–4.07) was the most frequent in the patients (p<0.05), and the Fy(a+b+) phenotype (p = 0.0039, OR = 1.71, 95% CI = 1.18–2.51) was the most frequent in the healthy subjects in the same region of Paraná state (p<0.05). Regarding HLA, the HLA-B*42, -B*45, -B*51 and -DRB1*03 allele groups were the most frequent in the patients (p<0.05), and the HLA-B*44 allele group was the most frequent in the healthy subjects in the same region of Brazil (p<0.05). The polymorphism of these two markers among CKD patients in southern Brazil and healthy subjects of other studies, suggests that these markers might be involved with CKD development. Further studies should be undertaken to analyze the markers'' influence on CKD and the long-term results from kidney transplantation.     

Correlation Between HLA-A,B and DRB1 Alleles and Severe Fever with Thrombocytopenia Syndrome

ObjectiveSevere fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever caused by a tick-borne bunyavirus (SFTSV) in East Asian countries. The role of human leukocyte antigen (HLA) in resistance and susceptibility to SFTSV is not known. We investigated the correlation of HLA locus A, B and DRB1 alleles with the occurrence of SFTS.MethodsA total of 84 confirmed SFTS patients (patient group) and 501 unrelated non-SFTS patients (healthy individuals as control group) from Shandong Province were genotyped by PCR-sequence specific oligonucleotide probe (PCR-SSOP) for HLA-A, B and DRB1 loci.Allele frequency was calculated and compared using χ² test or the Fisher''s exact test. A corrected P value was calculated with a bonferronis correction. Odds Ratio (OR) and 95% confidence intervals (CI) were calculated by Woolf’s method.ResultsA total of 11 HLA-A, 23 HLA-B and 12 HLA-DRB1 alleles were identified in the patient group, whereas 15 HLA-A, 30 HLA-B and 13 HLA-DRB1 alleles were detected in the control group. The frequencies of A*30 and B*13 in the SFTS patient group were lower than that in the control group (P = 0.0341 and 0.0085, Pc = 0.5115 and 0.252). The ORs of A*30 and B*13 in the SFTS patient group were 0.54 and 0.49, respectively. The frequency of two-locus haplotype A*30-B*13 was lower in the patient group than in the control group(5.59% versus 12.27%, P = 0.037,OR = 0.41, 95%CI = 0.18–0.96) without significance(Pc>0.05). A*30-B*13-DRB1*07 and A*02-B*15-DRB1*04 had strong associations with SFTS resistance and susceptibility respectively (Pc = 0.0412 and 0.0001,OR = 0.43 and 5.07).ConclusionThe host HLA class I polymorphism might play an important role with the occurrence of SFTS. Negative associations were observed with HLA-A*30, HLA-B*13 and Haplotype A*30-B*13, although the associations were not statistically significant. A*30-B*13-DRB1*07 had negative correlation with the occurrence of SFTS; in contrast, haplotype A*02-B*15-DRB1*04 was positively correlated with SFTS.     

Ancestral association between HLA and HFE H63D and C282Y gene mutations from northwest Colombia

A significant association between HFE gene mutations and the HLA-A*03-B*07 and HLA-A*29-B*44 haplotypes has been reported in the Spanish population. It has been proposed that these mutations are probably connected with Celtic and North African ancestry, respectively. We aimed to find the possible ancestral association between HLA alleles and haplotypes associated with the HFE gene (C282Y and H63D) mutations in 214 subjects from Antioquia, Colombia. These were 18 individuals with presumed hereditary hemochromatosis (“HH”) and 196 controls. The HLA-B*07 allele was in linkage disequilibrium (LD) with C282Y, while HLA-A*23, A*29, HLA-B*44, and B*49 were in LD with H63D. Altogether, our results show that, although the H63D mutation is more common in the Antioquia population, it is not associated with any particular HLA haplotype, whereas the C282Y mutation is associated with HLA-A*03-B*07, this supporting a northern Spaniard ancestry.     

Molecular analysis of human leukocyte antigen class I and class II allele frequencies and haplotype distribution in Pakistani population

AIM:

Distribution of HLA class I and II alleles and haplotype was studied in Pakistani population and compared with the data reported for Caucasoid, Africans, Orientals and Arab populations.

MATERIALS AND METHODS:

HLA class I and II polymorphisms in 1000 unrelated Pakistani individuals was studied using sequence-specific primers and polymerase chain reaction and assay.

RESULTS:

The most frequent class I alleles observed were A*02, B*35 and CW*07, with frequencies of 19.2, 13.7 and 20%, respectively. Fifteen distinct HLA-DRB1 alleles and eight HLA-DQB1 alleles were recognized. The most frequently observed DRB1 alleles which represented more than 60% of the subjects were DRB1 *03, *07, *11 and *15. The rare DRB1 alleles detected in this study were HLADRB1 *08 and *09, having frequencies of 0.9 and 1.7%, respectively. In addition, at DRB1-DQB1 loci there were 179 different haplotypes and 285 unique genotypes and the most common haplotype was DRB1*15-DQB1*06 which represented 17% of the total DRB1-DQB1 haplotypes. In our population, haplotype A*33-B*58-Cw*03 comprised 2.8% of the total class I haplotypes observed. This haplotype was seen only in the oriental populations and has not been reported in the African or European Caucasoid.

CONCLUSION:

Our study showed a close similarity of HLA class I and II alleles with that of European Caucasoid and Orientals. In Pakistani population, two rare loci and three haplotypes were identified, whereas haplotypes characteristic of Caucasians, Africans and Orientals were also found, suggesting an admixture of different races due to migration to and from this region.     

HLA genes and haplotypes in Ryukyuans suggest recent gene flow to the Okinawa Islands.

Polymorphism of HLA genes was investigated in a population sample of Ryukyuans living on the main island of Okinawa (n = 197), in the southwestern islands of Japan. Serological typing was applied to class I loci (HLA-A, -B, and -C) and to HLA-DRB1; nucleotide sequence-level typing was performed using PCR microtiter plate hybridization and PCR single-strand conformation polymorphism methods. Ryukyuans showed a higher frequency of DRB1*0405 and lower frequencies of DRB1*1502 and DRB1*1302 compared with Hondo Japanese living on main islands. Principal components and phylogenetic analyses of 12 East Asian populations, including Ryukyuans, were performed based on the allele frequencies of HLA-A, -B, and -DRB1. In the principal components analysis 3 Japanese populations (Ryukyuans, Hondo Japanese, and Ainu) formed a cluster and showed the highest affinity to 2 Korean populations. In the phylogenetic tree Ryukyuans and Ainu were neighbors, but the genetic distance between them was larger than the distances between Ryukyuans and Hondo Japanese and between Ryukyuans and Korean populations. The geographic cline of the predominant haplotype in Ryukyuans, A*24-B*54-DRB1*0405, suggests that an ancestral population possessing A*24-B*54-DRB1*0405 moved into the Okinawa Islands after the divergence of Ryukyuans from the Ainu. Such a recent gene flow, probably from South China to the Okinawa Islands, is considered the major cause of difference in genetic characteristics between Ryukyuans and the Ainu.