HLA class II allele and haplotype frequencies in Koreans based on 107 families

We have investigated the distribution of HLA class II alleles and haplotypes in 107 Korean families (207 parents and 291 children) for the HLA-DRB1, DRB3/B4/B5, DQA1, DQB1 and DPB1 loci. Numbers of alleles observed for each locus were DRB1: 25, DQA1: 14, DQB1: 15, and DPB1: 13. Only two to three alleles were observed for the DRB3 (*0101, *0202, *0301), DRB4 (*0103, * 0103102 N), and DRB5 (*0101, *0102) loci. These alleles showed strong associations with DRB1 alleles: DRB3*0101 with DRB1*1201, *1301 and *1403; DRB3*0301 with DRB1*1202 and *1302; DRB3*0202 with DRB1*0301, *1101, *1401 and *1405; DRB5*0101 and *0102 were exclusively associated with DRB1*1501 and *1502, respectively. The seven most common DRB1-DQB1 haplotypes of frequencies > 0.06 accounted for 52% of the total haplotypes. These haplotypes were exclusively related with the seven most common DRB1-DRB3/B4/B5-DQA1-DQB1 haplotypes: DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0602 (0.085), DRB1*0405-DRB4*0103-DQA1*0303-DQB1*0401 (0.082), DRB1*09012-DRB4*0103-DQA1*0302-DQB1*03032 (0.082), DRB1*0101-DQA1*0101-DQB1*0501 (0.075), DRB1*0701-DRB4*0103-DQA1*0201-DQB1*0202 (0.065), DRB1*0803-DQA1*0103-DQB1*0601 (0.065), and DRB1*1302-DRB3*0301-DQA1*0102-DQB1*0604 (0.065). When these haplotypes were extended to the DPB1 locus, much diversification of haplotypes was observed and only one haplotype remained with a frequency of > 0.06: DRB1*0405-DRB4*0103-DQA1*0303-DQB1*0401-DPB1*0501 (0.062). Such diversification would have resulted from cumulated events of recombination within the HLA class II region, and the actual recombination rate observed between the HLA-DQB1 and DPB1 loci was 2.3% (10/438 informative meioses, including 2 recombinants informative by analysis of TAP genes). Comparison of the distribution of DRB1-DQB1 haplotypes with other populations revealed that Koreans are closest to Japanese people. However, Koreans share a few haplotypes with white people and Africans, which are rare in Japanese: DRB1*0701-DQB1*0202 and DRB1*1302-DQB1*0609. The results obtained in this study will provide useful information for anthropology, organ transplantation and disease association studies.     

Polymorphism of HLA-A, -B, -DRB1, -DQA1 and -DQB1 haplotypes in a Croatian population.

We describe for the first time extended haplotypes in a Croatian population. The present study gives the HLA-A, -B, -DRB1, -DQA1 and -DQB1 allele and haplotype frequencies in 105 families with at least two offspring. All individuals were studied by conventional serology for HLA class I antigens (A and B), while class II alleles (DRB1, DQA1, DQB1) were typed using the PCR-SSOP method. HLA genotyping was performed by segregation in all 105 families. For extended haplotype analysis, 420 independent parental haplotypes were included. Fourteen HLA-A, 18 HLA-B, 28 DRB1, 9 DQA1 and 11 DQB1 alleles were found in the studied population. Most of the DRB1 alleles in our population had an exclusive association with one specific DQA1-DQB1 combination. This strong linkage disequilibrium within the HLA class II region is often extended to the HLA-B locus. A total of 10 HLA-A, -B, -DRB1, -DQA1, -DQB1 haplotypes were observed with a frequency 相似文献   

The distribution of HLA class II susceptible/protective haplotypes could partially explain the low incidence of type 1 diabetes in continental Italy (Lazio region)

HLA class II is the primary susceptibility gene to type 1 diabetes and the analysis of HLA class II association could help to clarify the relative weight of genetic contribution to the incidence of the disease. Here we present an extensive typing for HLA class II alleles and their haplotypes in a homogenous population of type 1 diabetic patients (n=134) and controls (n=128) and in simplex (n=100) and multiplex families (n=50) from continental Italy (Lazio region). Among the various haplotypes tested, the DRB1*0301-DQA1*0501-DQB1*0201 was the most frequent found in type 1 diabetic patients and was transmitted in 82% of affected siblings, whereas DRB1*0402-DQA1*0301-DQB1*0302 appeared to have the highest odds ratio (10.4), this haplotype was transmitted in 96.3% of affected siblings, followed by DRB1*0405-DQA1*0301-DQB1*0302, DRB1*0405-DQA1*0301-DQB1*0201, DRB1*0401-DQA1*0301-DQB1*0302 and DRB1*0404-DQA1*0301-DQB1*0302. The following haplotypes showed a significant decreased transmission to diabetic siblings: DRB1*0701-DQA1*0201-DQB1*0303, DR2-DQA1*01-DQB1*0602, DR5-DQA1*0501-DQB1*0301. We suggest that the HLA DR/DQ haplotype/genotype frequencies observed could in part explain the low incidence of type 1 diabetes registered in Lazio region (8.1/100.000/year), for a number of reasons: i) the low frequency, in the general control population, of the most susceptible haplotypes and genotype for type 1 diabetes DRB1*0301-DQA1*0501-DQB1*0201 (14%), and DR4-DQA1*0301-DQB1*0302 (9%) and DRB1*0301-DQA1*0501-DQB1*0201/DR4-DQA1*0301-DQB1*0302 (0.8%) compared to other countries characterised by high incidence rate of the disease, Sardinia and Finland, respectively; ii) a significant lower ratio, in the control population, between the susceptible DRB1*0301-DQA1*0501-DQB1*0201 and the neutral DRB1*0701-DQA1*0501-DQB1*0201 haplotypes compared to the Sardinian population; iii) the high frequency of protection haplotypes/genotypes as the DR5-DQA1*0501-DQB1*0301, and DR5-DQA1*0501-DQB1*0301/DR5-DQA1*0501-DQB1*0301 very common in the control population of Lazio region and the DRB1*1401-DQA1*0101-DQB1*0503 haplotype.     

Molecular analysis of HLA-DRB1, DQA1, DQB1, DQ promoter polymorphism and extended class I/class II haplotypes in the Seri Indians from Northwest Mexico

The study of the genetics of the Major Histocompatibility Complex (MHC) in Amerindians is of great value in understanding the origins and migrations of these native groups, as well as the impact of immunogenetics on the epidemiology of diseases affecting these populations. We analyzed, using Polymerase Chain Reaction and Sequence Specific Oligonucleotide Probes (PCR-SSOP), DRB1, DQA1, DQB1 alleles and the promoter regions of DQA1 and DQB1 genes in 31 unrelated and 24 related Seri, a Mexican Indian group, from the state of Sonora (Northwest Mexico). The class II genotypes of this population were found to be in genetic equilibrium. The allele frequency (AF) of the prevalent DRB1 alleles were DRB1*0407 (48.4%), DRB1*0802 (33.9%) and DRB1*1402 (16.1%). The most frequent DQA1 and DQB1 alleles were DQA1*03011 (AF = 50.00%), DQA1*0401 (AF = 33.87%) and DQA1*0501 (AF = 16.13%); DQB1*0302 (AF = 50.00%), DQB1*0402 (33.87%) and DQB1*0301 (16.13%); which were in combination with DRB1*0407, DRB1*0802 and DRB1*1402, respectively. Three QAP and three QBP alleles were present (QAP 3.1, 4.1, 4.2; QBP 3.1, 3.21, 4.1) associated with the typical published DQA1 and DQB1 alleles. Four class II haplotypes were present in family members: DRB1*0407-QAP-3.1-DQA1*03011-QBP-3.21-DQB1*0302; DRB1*0802-QAP-4.2-DQA1*0401-QBP-4.1-DQB1*0402; DRB1*1402-QAP-4.1-DQA1*0501-QBP-3.1-DQB1*0301 and DRB1*0701-QAP-2.1-DQA1*0201-QBP-2.1-DQB1*0201. The family data were used to confirm extended haplotypes. A total of 21 haplotypes were found when A* and B* loci were also considered. The three most frequent combinations included A*0201-B*3501-DRB1*0407, A*3101-B*5101-DRB1*0802, and A*0201-B*40-DRB1*1402.     

Striking conservation of three extended HLA-DR13 haplotypes in the Japanese population

Abstract: HLA class II DNA typing was conducted for 1335 unrelated Japanese individuals. The study on the linkage disequilibrium revealed a striking conservation of HLA DR13 haplotypes. Among these Japanese, 155 were typed for HLA-DR13 serologically, and they were correspondent to three DRB1 alleles, DRB1*1301, 1302 and 1307 defined by using the polymerase-chain reaction and sequence-specific oligonucleotide probe (PCR-SSOP) method. The two alleles, DRB1*1301 and 1307 were exclusively associated with each specific DRB3-DQA1-DQB1 combination which was DRB1*1301-DRB3*0101-DQA1*0103-DQB1*0603, and DRB1*1307-DRB3*0202-DQA1*0501-DQB1*0301, respectively. DRB1* 1302, the most common DR13 allele in Japanese, had two significant associations with DRB3*0301-DQA1*0102-DQB1*0604 (DRB1*1302A) and with DRB3*0301-DQA1*0102-DQB1*0605 (DRB1*1302B). In this study, no other DR13 class II combinations were found. Ony the DRB1*1302A halotype was associated with the DPB1*0401 allele while the DRB1*1302B haplotype was not. The complete conservation of these DR13 class II haplotypes was found to extend toward the HLA class I region. They were HLA A3-B44-DRB1*1301, A33-B44-DRB1*1302A and A33-B17-DRB1*1302B. Japanese could be characterized with these three extended haplotypes which were remakrably different from those in Caucasian, Black and Asian other than Korean populations.     

HLA class II immunogenetics and incidence of insulin-dependent diabetes mellitus in the population of Cantabria (Northern Spain)

HLA class II genes were analyzed to study IDDM susceptibility in Cantabria (Northern Spain). Patients showed highly significant increases in DRB1*0301 (RR = 4.581, p < 0.00005), DRB1*0401 (RR = 2.6, p < 0.05), DRB1*0402 (RR = 8.78, p < 0.05) and DRB1*0405 (RR = 14.73, p < 0.005). Highly significant diferences were in the DQA1*0301 (RR = 3.62, p < 0.000005) and DQA1*0501 (RR = 2.13, p < 0.05) alleles. DQB*0201 (RR = 4.1, p < 0.00005) and DQB1*0302 (RR = 5.42, p < 0.000005) alleles were also significantly increased. A significant increase in DRB1*0402-DQA1*0301-DQB1*0302 (RR = 16.18, p < 0.05), DRB1*0405-DQA1*0301-DQB1*0302 (RR = 16.12, p < 0.05), DRB1*0301-DQA1*0501-DQB1*0201 (RR = 4.58, p < 0.00005) and DRB1*0401-DQA1*0301-DQB1*0302 (RR = 4.36, p < 0.005) was apparent in the diabetic group, while the DRB1*1501-DQA1*0102-DQB1*0602 and DRB1*1401-DQA *0104-DQB1*05031 protective haplotypes (RR = 0.17 and 0.09, p < 0.0005 and 0.05, respectively) were significantly lower in patients. The absence of Asp57 and the presence of Arg52 were associated with disease in a dose-dependent manner. Several genotypes encoding the identical DQalpha52/DQbeta57 phenotype carried very different RRs. Finally, the Cantabrian population has the highest incidence of IDDM reported for Spain (15.2 of 100.000 in the 0-14 age group, Poisson's 95% CI: 10.6-19.3).     

HLA class II antigens in South African Blacks with type I diabetes

Type 1 diabetes mellitus is poorly characterised in many African communities, including South Africa, where little is known of the disease epidemiology. This study aimed to identify the HLA class II alleles associated with type 1 diabetes in a group of Zulu subjects in Durban, KwaZulu-Natal by PCR-SSP. The HLA alleles associated with type 1 diabetes included HLA-DQB*0302 (P<0.0001), DRB1*O9 (P<0.0001), DRB1*04 (P=0.002), DRB1*0301 (P=0.003), DQB*02 (P=0.004) and DQA*03 (P=0.035). Estimated haplotypes positively associated with type 1 diabetes included HLA-DRB1 *0301-DQA*0501, DRB1*04-DQA*03, DRB1*04-DQB*0302, DRB1*0301-DQB*0201, DQA*0501-DQB*0201 and DQA*03-DQB*0302. These findings are similar to those reported from Zimbabwe and other populations with type 1 diabetes.     

Molecular analysis of HLA class II polymorphism in Croatians

Abstract: HLA-class II polymorphisms have been studied in a population of 141 unrelated healthy Croatians using PCR amplification, followed by non-radioactive oligonucleotide hybridization. Thirty one DRB1, 8 DQA1, 13 DQB1 and 16 DPB1 alleles were found in the tested population. DRB1*1601, 0701, 1501, 0101 and 1104 are the most frequent alleles at the DRB1 locus. At the DQA1 locus two alleles predominate: DQA1*0501 and 0102, while the most frequent DQB1 allele is *0301. Analysis of HLA-DPB1 polymorphism showed that, as in other Europeans, DPB1* 0401 is the most frequent allele. Four different two locus haplotypic associations (DRB1-DRB3, DRB1-DRB5, DRB1-DQB1 and DQA1-DQB1) as well as three locus DRB1-DQA1-DQB1 haplotypic associations were assigned on the basis of known linkage disequilibria. Several unusual two-locus associations have been observed: DRB1*0301-DRB3* 0202, DRB1*1501-DRB5*02, DRB1*1601-DRB5*0101, DRB1*1502-DRB5*0101, DQA1*0103-DQB1*0503 and DQA1*0501-DQB1*0302. Among 236 examined DRB1-DQA1-DQB1 haplotypic combinations, the most frequent was DRB1*1601-DQA1*0102-DQB1*0502 that was found with statistically significant higher frequency than in other Europeans. Twenty-eight distinct probable haplotypes were observed just once, suggesting that the main characteristic of Croatian population is great heterogeneity of haplotypes. This study will serve as a reference for further anthropology studies, HLA and disease associations studies and for donor/recipient matching in organ and bone marrow transplantation.     

Molecular analysis of HLA allele frequencies and haplotypes in Baloch of Iran compared with related populations of Pakistan

The extreme polymorphism in different loci of the human leukocyte antigen (HLA) system has been used as an invaluable tool for anthropological studies. Determination of HLA allele and haplotype frequencies in different ethnic groups is useful for population genetic analyses and the study of genetic relationships among them. In the present study, molecular analysis of HLA-A, -B, -C, -DQA1, -DQB1, and -DRB1 genes has been used to assign HLA allele and haplotype frequencies in 100 unrelated healthy individuals from the Baloch ethnic group of Iran. The results were compared with Baloch and other ethnic groups in the neighboring Pakistan. The results of this study showed that the most frequent HLA class I alleles were A*02011 (20.2%), B*4006 (11.1%), and C*04011 (28.6%). The most common HLA class II alleles were DQA1*0101/2 (42.5%), DQB1*0201 (32%), and DRB1*0301 (29%). Three-locus haplotype analysis revealed that A*11011-B*4006-C*15021 (5.8%) and DQA1*0501-DQB1*0201-DRB1*0301 (22.1%) were the most common HLA class I and II haplotypes, respectively, in this population. Neighbor-joining tree based on DA genetic distances and correspondence analysis according to HLA-A, -B, -DQB1, and -DRB1 allele frequencies showed that Baloch of Iran are genetically very close to Baloch and Brahui of Pakistan. This may reflect an admixture of Brahui and Baloch ethnic groups of Pakistan in the Balochistan province of Iran.     

The HLA class I and class II allele frequencies studied at the DNA level in the Svanetian population (Upper Caucasus) and their relationships to Western European populations

The Caucasus and the Iberian peninsula have been connected from a linguistic (Basque and Kvartelian languages), toponimic and historic perspectives. They also represent places (e.g. Dmanisi in Georgia and Atapuerca in Northern Spain) where the oldest hominoid remains in Europe are being discovered and studied. These circumstances prompted us to study the genetic background of the Svans (living on the southern slopes of the Greater Caucasus in the Republic of Georgia) in comparison with Basques from the semi-isolated Arratia valley as well with other Northern Spanish and Western European populations. DRB1*1101-DQA1*0501-DQB1*0301 and DRB1*1301-DQA1*0103-DQB1*0603 haplotypes were found in Svans at the highest frequency. The second most frequent three-locus haplotypes in this population were DRB1*0701-DQA1*0201-DQB1*0201 and DRB1*1301-DQA1*0103-DQB1*0602. Furthermore, the following 5-locus extended haplotypes were not found in other populations: A3-B8-DRB1*11-DQA1*0501-DQB1*0301, A2-B8-DRB1*13-DQA1*0103-DQB1*0603, A2-B40-DRB1*14-DQA1*0104-DQB1*0501, A2-B51-DRB1*08-DQA1*0401-DQB1*0402, A3-B7-DRB1*03-DQA1*0501-DQB1*0201 and A24-B39-DRB1*08-DQA1*0401-DQB1*0402. Other haplotypes present in Svans were also frequently observed in Northern Spain and in other Western European countries. However, haplotypes reported as characteristic for Basques were not found in the Svans. A dendrogram using HLA class II alleles places the closest genetic distance observed between Svans and Czechs, whereas Slovenes and other Mediterranean populations (Jews, Hungarians, Frenchmen, Sardinians and Greeks) have the greatest genetic distance. When both HLA class I and class II alleles from 17 populations were compared, the smallest genetic distances were with Rumanians, Czechs and Armenians. Northern Spanish populations were placed closer to each other and clearly separated from Svans. In conclusion, the Svan population shows considerable polymorphism. These observations suggest a mixture of alleles in Svans from geographically distinct areas, and probably do not support a common ancestor for these Caucasian inhabitants and people from Northern Spain.     

HLA Class II (DRB,DQA1 and DQB1) Allele and Haplotype Frequencies in the Patients with Pemphigus Vulgaris

Introduction  Pemphigus vulgaris (PV), an autoimmune disease affecting the skin and mucous membranes, is associated with some human leukocyte antigen (HLA) class II alleles and haplotypes. Materials and Methods  In order to evaluate the association of HLA-DR and DQ alleles and haplotypes in Iranian non-Jewish patients with PV, 52 patients with PV and 180 normal subjects as control group were investigated in this study. Results and Discussion  HLA-DRB1*04, -DRB1*1401, -DRB4, -DQA1*0104, -DQA1*03011, -DQB1*0302, and -DQB1*0502 alleles have been significantly increased in our patients group. Moreover, the haplotypes HLA-DRB1*04/-DQA1*03011/-DQB1*0302 and HLA-DRB1*1401/-DQA1*0104/-DQB1*0502 increased significantly in our patients. In contrast, the following alleles decreased significantly in our patients: HLA-DRB1*15, -DRB1*0301, -DRB1*07, -DRB1*11, -DRB5, -DQA1*0101, -DQA1*0103, -DQA1*201, -DQA1*05, -DQB1*0201, -DQB1*0301, -DQB1*06011, and -DQB1*0602. In addition, HLA-DRB1*15/-DQA1*0103/-DQB1*06011, HLA-DRB1*0301/-DQA1*05011/-DQB1*0201, HLA-DRB1*07/-DQA1*0201/-DQB1*0201, and HLA-DRB1*11/-DQA1*05/-DQB1*03011 decreased significantly in our patients. Genetic factors are involved in the occurrence of PV; HLA-DRB1*04 and -DRB1*1401 alleles and the related haplotypes are suggestive to be two major PV susceptibility factors in our population study.     

HLA polymorphism in the Murcia population (Spain): in the cradle of the archaeologic Iberians.

Human leukocyte antigen (HLA) study in Murcian individuals was performed in order to provide information of their historical origins and relationships with other Iberian and Mediterranean populations. HLA class I and class II alleles were determined in 173 unrelated Caucasoid donors from Murcia Region in the Southeast of Spain by serologic and DNA based polymerase chain reaction (PCR) typing. Class I antigen and class II allele frequencies of our series were not very different to those found in Spaniards. The analysis of extended haplotypes showed that the three haplotypes most frequent in our population were respectively, A29-B44-Cwb-DRB1*0701-DRB4*0101-DQA1*0201-DQB1*0202, A1-B8-Cw7-DRB1*0301-DRB3*0101-DQA1*0501-DQB1*0201 and A30-B18-Cw5-DRB1*0301-DRB3*0101-DQA1*0501-DQB1*0201. They were followed by A26-B38-Cwb-DRB1*1301-DRB3*0202-DQA1*0103-DQB1*0603, which could point to an ancestral relationship between Murcian and Portuguese Iberian populations, and by A2-B7-Cw7-DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0602 also present in all Iberian Peninsula populations. Allelic frequencies, populations distance dendrogram and correspondence analysis were used to study the relationships between Murcian and other populations. The closest relation was observed with Spaniards and Portuguese, followed in decreasing order by French, Italians, Algerians, Germans, Catalans, Basques, Cretans, Sardinians, and Greeks. Thus, Murcian population seems to belong to the European genetic pool, revealing a lesser genetic distance with the North Africans and the rest of populations from the Iberian Peninsula.     

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.     

HLA-associated genetic resistance and susceptibility to type I diabetes in French North Africans and French natives

The distribution of human leukocyte antigen (HLA)-DRB1-DQA1-DQB1 haplotypes was analyzed separately in two distinct French ethnic groups with type I diabetes (T1D), i.e. French North African migrants (n= 64, mean age at diagnosis = 8.25 years) and ancient French natives (n= 60, mean age at diagnosis = 7.42 years). HLA associations were determined by calculating odds ratios (ORs) between patients and two ethnic-matched control populations. Results show highly similar ORs for the conservative DRB1*0301-DQA1*0501-DQB1*0201 haplotype of susceptibility (OR: 3.22 and 3.93 in migrants and natives, respectively) and the DRB1*1501-DQA1*0102-DQB1*0602 haplotype of resistance (OR: 0.05 and 0.03, respectively). In contrast, among the more variable DRB1*04-DQB1*0302 haplotypes of susceptibility, the DRB1*0402 (OR: 3.10 and 32.84) and 0405 (OR: 5.90 and 16.25, respectively) were associated with T1D in migrants and natives, whereas an increase of DRB1*0401, a rare allele in migrants, was significant in natives only. Also, among the DRB1*11-DQA1*0505-DQB1*0301 haplotypes of resistance, the OR observed for DRB1*1104-DQA1*0505-DQB1*0301, common in migrants, was lower (OR: 0.08) than for DRB1*1101-DQA1*0505-DQB1*0301 (OR: 0.32), common in natives. How DRB1*11 subtypes might affect differently the risk conferred by DQA1*0505-DQB1*0301 will be discussed.     

Distribution of HLA Class II Alleles and Haplotypes in Mexican Mestizo Population: Comparison with Other Populations

We describe the analysis of the Major Histocompatibility Complex (MHC) class II polymorphism in Mexican Mestizo population. The study provides the HLA-DRB1, DQA1 and DQB1 allele frequencies in 99 Mexican Mestizos. DNA from these individuals was typed by PCR followed by hybridization using sequence specific oligonucleotides (PCR-SSO). The relationship with other worldwide populations was studied by using HLA data from 69 different populations and calculating neighbor-joining dendrograms and correspondence multidimensional values. The highest frequencies were for DRB1*0802 (allele frequency = 0.151), DRB1*0701 (allele frequency = 0.111) and DRB1*0407 (allele frequency = 0.106). Among the eight DQA1 alleles detected, the most frequent were DQA1*03011 (allele frequency = 0.257), DQA1*0501 (allele frequency = 0.227) and DQA1*0401 (allele frequency = 0.166). Twelve DQB1 alleles were found and four of them, DQB1*0302 (allele frequency = 0.237), DQB1*0301 (allele frequency = 0.176), DQB1*0201 (allele frequency = 0.166) and DQB1*0402 (allele frequency = 0.166) showed the highest frequencies. The haplotype DRB1*0802-DQA1*0401-DQB1*0402 (0.151) predominated clearly, followed by DRB1*0701-DQA1*0201-DQB1*0201 (0.111) and DRB1*0407-DQA1*03011-DQB1*0302 (0.101). Both genetic distances and correspondence analyses showed that Mexicans clustered with Amerindian population. These results suggest that the Mexican Mestizo population be principally characterized by haplotypes presents in Amerindian and Caucasian populations with a low frequency of Black haplotypes. In summary, the HLA class II haplotype frequencies demonstrated the tri-racial component existing in Mexican Mestizos.     

Distribution of HLA class II alleles and haplotypes in insulin-dependent moroccan diabetics

HLA class II polymorphism in Moroccan IDDM patients has not been investigated so far. In this study, HLA-DRB1, -DQA1, and -DQB1 allele and haplotype frequencies were analyzed in 125 unrelated Moroccan IDDM patients and 93 unrelated healthy controls, all originating from the Souss region and mostly of Berber origin. Some common features with other Caucasian groups were observed, in particular, a predisposing effect of the DRB1^*03-DQA1^*0501-DQB1^*0201 and DRB1^*04-DQA1^*0301-DQB1^*0302 alleles or allelic combinations. The Moroccan IDDM group also presented with more specific characteristics. Among DRB1^*04 subtypes, DRB1^*0405 was associated with susceptibility to and DRB1^*0406 with protection from the disease. The haplotype and the relative predispositional effect (RPE) analyses indicated that the DRB1^*08-DQA1^*0401DQB1 ^*0402 haplotype was also associated with susceptibility to IDDM. Interestingly, the DRB1^*09DQA1 ^*0301-DQB1^*0201 haplotype, completely absent from the control group and very rare in North African populations, was observed in 7.2% of the Moroccan diabetics. Conversely, the DRB1^*07-DQA1^*0201DQB1 ^*0201 and DRB1^*15-DQA1^*0102-DQB1^*0602 haplotypes were associated with protection from IDDM. Finally, we observed an age-dependent genetic heterogeneity of IDDM, the frequencies of predisposing alleles being higher and those of protective alleles lower in childhood- than in adult-onset diabetics. Our data on Moroccan diabetics, together with data on European and Northern Mediterranean patients, suggest a gradient of various HLA class II predisposing and protective markers that link these populations     

HLA DR-DQ-encoded genetic determinants of childhood-onset type 1 diabetes in Finland: an analysis of 622 nuclear families

The diabetes predisposing effect of HLA genes is defined by a complex interaction of various haplotypes. We analyzed the disease association of HLA DRB1-DQA1-DQB1 genotypes in a large nuclear family cohort (n = 622) collected in Finland. Using the affected family based artificial control approach we aimed at characterizing all detectable disease-specific HLA haplotype and genotype effects. The DRB1*0401-DQB1*0302 haplotype was the most prevalent disease susceptibility haplotype in the Finnish population followed by (DR3)-DQA1*05-DQB1*02 and DRB1*0404-DQB1*0302. DRB1*0405-DQB1*0302 conferred the highest disease risk, although this haplotype was very rare. The DRB1*04-DQB1*0304 was also associated with increased disease risk, an effect detected for the first time in the Finnish population. The following haplotypes showed significant protection from the disease and are listed in decreasing order of the strength of their effect: (DR7)-DQA1*0201-DQB1*0303, (DR14)-DQB1*0503, (DR15)-DQB1*0602, DRB1*0403-DQB1*0302, (DR13)-DQB1*0603, (DR11/12/13)-DQA1*05-DQB1*0301, (DR1)-DQB1*0501. In addition to the DRB1*0401/0404-DQB1*0302/(DR3)-DQA1*05-DQB1*02 genotype and DRB1*04-DQB1*0302 homozygous genotypes, heterozygous combinations DRB1*0401-DQB1*0302/(DR13)-DQB1*0604, approximately /(DR8)-DQB1*04, approximately /(DR9)-DQA1*03-DQB1*0303, approximately /(DR1)-DQB1*0501 and approximately /(DR7)-DQA1*0201-DQB1*02 were also disease-associated. As a new finding in this population, the (DR3)-DQA1*05-DQB1*02 homozygous and (DR3)-DQA1*05-DQB1*02/(DR9)-DQA1*03-DQB1*0303 heterozygous genotypes conferred disease susceptibility. Similarly, the DRB1*0401-DQB1*0302/(DR13)-DQB1*0603 genotype was disease predisposing, implying that DQB*0603-mediated protection from diabetes is not always dominant. Comparison of our findings with published data from other populations indicates a significant disease-specific heterogeneity of the (DR8)-DQB1*04, (DR7)-DQA1*0201-DQB1*02 and (DR3)-DQA1*05-DQB1*02 haplotypes.     

Association between autoantibody markers and subtypes of DR4 and DR4-DQ in Swedish children with insulin-dependent diabetes reveals closer association of tyrosine pyrophosphatase autoimmunity with DR4 than DQ8

Abstract: HLA DQA1*0301-DQB1*0302 (DQ8) and DQA1*0501-DQB1*0201 (DQ2) are positively and DQA1*0102-DQB1*0602 (DQ6) negatively associated with IDDM. In DQA1*0301-DQB1*0302 (DQ8)-positive patients, susceptibility is also mediated by DRB1*0401. The aim of the study was to determine the association between HLA-DR4 and DQ and the presence of GAD65, ICA512, and insulin autoantibodies as well as ICA in 425 Swedish children with IDDM and 367 controls in the age group of 0–15 years. We found that ICA512 autoantibodies were associated primarily with DRB1*0401 and not with DQA1*0301-DQB1*0302 (DQ8). No such hierarchy could be demonstrated for insulin autoantibodies, which were associated with both DQA1*0301-DQB1*0302 (DQ8) and DRB1*0401. GAD65 autoantibodies, known to be closely associated with DQA1*0501-DQB1*0201 (DQ2)-DRB1*0301 haplotype, also showed no preferential association with DQA1*0301-DQB1*0302 (DQ8) versus DRB1*04. These results suggest that the immune response to different β-cell autoantigens may be mediated via HLA class II molecules from different loci. Design of the antigen-specific immuno-intervention trials should take into account these HLA-DR and DQ subtype associations.     

Molecular analysis of HLA polymorphism in Khoton-Mongolians

We have investigated polymorphism of the HLA class I and class II genes in Mongolians for the first time using PCR-based techniques. A minor population of Khoton-Mongolians was studied and compared to the major Khalkh-Mongolian population. Eighty-five Khoton-and 41 Khalkh-Mongolian samples were analyzed for polymorphism in HLA-A, -B, -DRB1, -DRB3, -DRB5, -DQA1, -DQB1, -DPA1, and -DPB1 loci using PCR-SSOP and PCR-RFLP methods. Allele and haplotype frequencies were calculated. The results were then compared to those obtained from other human populations. In Khoton-Mongolians, the frequency of HLA-B38, DRB1*0301, DQA1*0502, DQB1*0201 and DPB1*0401 were significantly higher than those in other Mongoloid populations including Khalkh-Mon-golians, Buryat, Chinese, Northern Han, Southern Han, Koreans and Japanese. In contrast, the frequency of HLA-A2, DQA1*0102, DPB1*0201 and DPB1*0501 were significantly lower in Khoton-Mongolians. Haplotype frequency analysis revealed that Khoton-Mongolians shared the same haplotypes specific to Mongoloids as well as to Caucasoids. On the other hand, several haplotypes were found to be specific for the Khoton. The phylogenetic tree analysis constructed by the NJ method based on allele frequencies of HLA-A, -B, -DRB1, -DQA1, and -DQB1 genes revealed that the Khoton belong to the Northeast Asian cluster and are most closely related to the Khalkh, Inner Mongolian, Uygur and Buryat populations. These data suggest a unique genetic background for Khoton-Mongolians. Furthermore, they are closely related genetically to both Mongoloids and Caucasoids.