HLA-DR2 HAPLOTYPIC DIVERSITY IN POPULATIONS OF SOUTH-EAST ASIA,NORTHERN CHINA,MELANESIA AND AUSTRALIAN ABORIGINES USING PCR-RFLP FOR DRB1, DRB5, DQA1 AND DQB1. A NOVEL DRB1 ALLELE: DRB1 * 16022

The polymorphism of the human leucocyte antigen HLA-DR2 and the heterogeneity of HLA-DR2 class II-related haplotypes (HLA-DRB1-DRB5-DQA1-DQB1) were investigated in four populations of east and south-east Asia (SEA) and five Melanesian populations using TaqI restriction fragment length polymorphism (RFLP) analysis, and the polymerase chain reaction (PCR) amplification-based techniques PCR-RFLP and sequence-specific oligonucleotide (SSO) typing. The haplotype DRB1*1502-DRB5*0101-DQA1*0102-DQB1*0601 was common in Malaysians, Javanese, Thursday Islanders, Madang, Goroka and the Australian Aborigines, while DRB1*16021-DRB5*0101-DQA1*0102-DQB1*0502 was common in the Thai and Thursday Islanders. DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0602 was present at a high frequency in Northern Chinese, Goroka, Watut and Australian Aborigines. The study describes four rare or unusual haplotypes: HLA-DRB1*1501-DRB5*0101-DQA1*0101-DQB1*0601, DRB1*1502-DRB5*0101-DQA1*0101-DQB1*0502, DRB1*1502-DRB5*0102-DQA1*0102-DQB1*0502 and DRB1*1501-DRB5*0101-DQA1*0101/2-DQB1*0503; the latter two were confirmed by segregation in two Javanese families. A new DR2 allele, initially detected by PCR-RFLP and confirmed by DNA sequencing as DRB1 * 16022 (previously designated DRB1 * 16Madang), was seen in a Madang individual. A new HLA-DR2 TaqI RFLP subtype, locally designated as DR15U, is also described. This RFLP subtype segregated in a Javanese family and correlated with a typically SEA haplotype, DRB1*1502-DRB5*0102-DQA1*0101-DQB1*0501. The allele HLA-DR16Thai, determined by TaqI DRB RFLP, was found by PCR-RFLP and SSO typing to correlate with a unique SEA haplotype, HLA-DRB1*16021-DRB5*0101-DQA1*0102-DQB1*0502, and was observed in the Thai, Malaysian, Thursday Islander, Javanese and Northern Chinese populations.     

Diversity in HLA-DR4-related DR,DQ haplotypes in Australia, Oceania, and China

The relative distributions of 12 HLA-DR4-related DRB1 alleles in indigenous populations of Australia, Melanesia, Micronesia, Polynesia, and northern and southern China have been determined by analysis of oligonucleotide hybridization patterns of 406 examples of HLA-DR4. DRB1^*0405 and DRB1^*0410 were common DR4 alleles in Australian aborigines and in Melanesians, while DRB1^*0403 was the predominant DR4 allele in coastal Melanesians, Micronesians, and Polynesians; DRB1^*0406 was confined to Chinese. A novel DR4 allele, found in 30% of DR4-positive Australian aborigines but exclusive to one aboriginal population, was a combination of DRB1^*04 and 0803 nucleotide sequences and was carried on a haplotype with DR4-like DQ linkage arrangements. DQA1 and DQB1 typing generated 12 DR4-related haplotypes; the population distributions of these reflected the ancestral affinities of aborigines and Melanesians, the overlaping of coastal Melanesia with pre-Polynesian DR4 alleles and the colonization of Micronesia by an independent, non-Polynesian group. DR4-related autoimmune disorders such as rheumatoid arthritis (RA) and insulin-dependent diabetes mellitus (IDDM) are virtually unknown in indigenous populations of Australian and Oceania and this study confirmed that high-risk RA determinants, Dw4 and Dw14, occurred rarely. However, the DQw8 allele, thought particularly to predispose to IDDM, was present in the majority of DR4-positive Polynesians and Micronesians.     

HLA class II (DRB1, DQA1 and DQB1) associated genetic susceptibility in Iranian multiple sclerosis (MS) patients

The association of HLA class II alleles with multiple sclerosis (MS) has been amply documented. In the present study, the role of HLA class II (DRB1, DQA1 and DQB1) alleles and haplotypes was investigated in 43 unrelated Iranian chronic progressive multiple sclerosis (CP-MS) patients compared with 100 healthy individuals. HLA typing for DRB1, DQA1 and DQB1 was performed by restriction fragment length polymorphism (RFLP). Subtypes of DR4, DR15 and DR16 were defined using polymerase chain reaction (PCR) amplification with sequence-specific primers (PCR-SSP). The results show that, among DR2-positive MS patients and the control group, a positive association with the DRB1*1503, DQA1*0102, DQB1*0602 haplotype (21% vs. 2.7%, P=0.057, RR=9.8) and a negative association with the most frequent DR15 haplotype in the control group, DRB1*15021, DQA1*0103, DQB1*0601 (7% vs. 24.3%, P=0.001), were observed. No significant association was found with the analysed HLA-DRB1, DQA1 and DQB1 alleles.     

HLA-DR AND -DQB1 DNA POLYMORPHISMS IN A VIETNAMESE KINH POPULATION FROM HANOI

We report here the DNA polymerase chain reaction sequence-specific oligonucleotide (PCR-SSO) typing of the HLA-DR B1, B3, B4, B5 and DQB1 loci for a sample of 103 Vietnamese Kinh from Hanoi, and compare their allele and haplotype frequencies to other East Asiatic and Oceanian populations studied during the 11th and 12th International HLA Workshops. The Kinh exhibit some very high-frequency alleles both at DRB1 (1202, which has been confirmed by DNA sequencing, and 0901) and DQB1 (0301, 03032, 0501) loci, which make them one of the most homogeneous population tested so far for HLA class II in East Asia. Three haplotypes account for almost 50% of the total haplotype frequencies in the Vietnamese. The most frequent haplotype is HLA-DRB1*1202-DRB3*0301-DQB1*0301 (28%), which is also predominant in Southern Chinese, Micronesians and Javanese. On the other hand, DRB1*1201 (frequent in the Pacific) is virtually absent in the Vietnamese. The second most frequent haplotype is DRB1*0901-DRB4*01011-DQB1*03032 (14%), which is also commonly observed in Chinese populations from different origins, but with a different accessory chain (DRB4*0301) in most ethnic groups. Genetic distances computed for a set of Asiatic and Oceanian populations tested for DRB1 and DQB1 and their significance indicate that the Vietnamese are close to the Thai, and to the Chinese from different locations. These results, which are in agreement with archaeological and linguistic evidence, contribute to a better understanding of the origin of the Vietnamese population, which has until now not been clear.     

HLA class II gene polymorphism in Tunisians

Abstract: The polymorphism of HLA clas II genes (HLA-DRB, DQB, DPB) was investigated in 101 Tunisians using polymerase chain reaction (PCR) amplification and reverse dot blot (RDB) hybridization. Allele and haplotype frequencies, as well as DRB1-DQB1 linkage disequilibria, were calculated. A total of 26 DRB1 alleles were detected and the most prevalent variant was DRB1*0301 with an allelic frequency at 21.87%. In the DR1 group, DRB1*0102 was most frequent than DRB1*0101. In the DR4 group, DRB1*0403 was the most common allele and was associated with DQB1*0402. Interestingly this DRB 1-DQB1 association has not been observed in other populations. With regard to the DR8 group, DRB1*0804 was the unique variant detected, whereas with the DR13 specificity, the most common variant was DRB1*1303 in Algerians also. Although the DQB1 polymorphism analysis showed an allelic distribution very close to that observed in caucasoids, many DRB1-DQB1 associations which have not been reported in studies of other populations, were described. Finally at the DPB1 locus DPB1*1701 and *1301 allele frequencies distinguish clearly this Tunisian sample from a French caucasoïd panel of 83 subjects. In conclusion, a specific distribution of HLA components in terms of gene and haplotype frequencies characterizises this Tunisian population. This specific pattern may reflect the great ethnic diversity of this community. All these informations may be helpful in the future for HLA and disease association studies.     

Distribution of HLA class II alleles among Scandinavian patients with systemic lupus erythematosus (SLE): An increased risk of SLE among non[DRB1*03,DQA1*0501,DQB1*0201] Class II homozygotes?

HLA-DRB1, -DRB3, -DQA1 and -DQB1 alleles were determined by DNA typing in 51 Scandinavian patients with systemic lupus erythematosus (SLE) and 129 controls. DRB1*03,DRB3*0101,DQA1*0501,DQB1*0201 were significantly increased in the patient group, with relative risks (RR) of 2.80, 3.07, 3.55 and 2.12, respectively. These alleles are in strong linkage disequilibrium, and their possible relative contributions in predisposition to SLE are difficult to distinguish. The strongest association was found for DQA1*0501, which is in linkage disequilibrium with DRB1*03 as well as DRB1*11,12 (DR5). An increased frequency of DRB1*11,12 was observed (RR = 1.89, ns). No association with DRB1*15,16 (DR2) was found. The patients had a higher frequency of HLA class II homozygosity than the controls (RR = 5.05, p = 0.0005). When compared to the low-risk group (nonDRB1*03 class II heterozygotes), the cases homozygous for DRB1*03,DQA1*0501,DQB1*0201, known to be in linkage disequilibrium with the complement allele C4A*Q0, had the highest relative risk of developing SLE (RR = 16.39, p = 0.0002). However non[DRB1*03,DQA1*0501,DQB1*0201] class II homozygotes had a higher relative risk (RR = 4.68, p = 0.0147) than DRB1*03,DQA1*0501,DQB1*0201 heterozygotes, known to carry the C4A*Q0 allele (RR = 2.72, p = 0.0088). This may suggest that HLA class II molecules are directly involved in susceptibility to SLE.     

Variation of HLA class II genes in the Nganasan and Ket, two aboriginal Siberian populations.

Allelic frequencies at the three most polymorphic loci of the HLA class II region (DRB1, DQA1 and DQB1) were determined in the Nganasan and Ket, the remnants of the two most ancient groups in the Lower Yenisey River/Taimyr Peninsula region in northern Siberia. By single-stranded conformational polymorphism typing, verified by sequencing, 19 HLA-DRB1-DQA1-DQB1 haplotypes and 15 HLA-DRB1, seven DQA1 and 11 DQB1 alleles were found. The most frequent alleles were DRB1*1301 (23.5%), DQA1*0103 (29.4%), *0501/03/05 (29.4%), and DQB1*0301/09 (32.4%) in the Ket, and DRB1*0901 (25%), DQA1*0301 (39.6%), and DQB1*0301/09 (37.5%) in the Nganasan. The distribution patterns and comprehensive phylogenic analysis based on the haplotype frequencies of 17 Siberian populations suggest that the founders of both the Ket and the Nganasan came from Palaeolithic populations in the Altai-Sayan Upland.     

Complete cDNA sequences of the HLA-DRB1*14011, *1402, *1403 and *1404 alleles

Sequencing studies of HLA class II molecules have been focused almost exclusively on the highly polymorphic exon 2. In this study the complete cDNA sequence of four alleles of the DR14 lineage (DR52 group) are reported for the first time. The HLA-DRB1*1402 and *1403 sequences were shown to be identical to the previously determined DRB1*13011 sequence, also of the DR52 group, in exons 1, 3, 4, 5 and 6. HLA-DRB1*14011 and *1404 were identical to DRB1*13011 in exons 1, 4, 5 and 6 sequences while they showed specific features within their exon 3 sequence. Both alleles showed a synonymous substitution at the third base of codon 114. However, DRB1*14011 also has a non-synonymous substitution at the first base of codon 112 which results in a histidine to tyrosine substitution. This is a novel substitution as Histidine 112 is conserved in all known HLA class II B genes.     

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.     

Molecular genetic studies of HLA class II alleles in sarcoidosis

Abstract: Previous HLA serological studies showed positive associations of the DR52 antigen, the DR52-associated antigens (DR3, DR5 and DR6) and the DR8 antigen with sarcoidosis. To investigate the HLA alleles that may contribute to the genetic susceptibility to sarcoidosis at the DNA level, HLA-DRB1, -DRB3, -DQA1 and DQB1 genotyping using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was performed in 63 Japanese patients with sarcoidosis. The frequencies of the DR52-associated DRB1 alleles (DRB1*11, DRB1*12 and DRB1*14 except DRB1*1302), DRB1*08, DRB3*0101, DQA1*0501 and DQB1*0301 were significantly increased in patients compared with healthy controls. The significant increase of DRB3*0101, DQA1*0501 and DQB1*0301 could be explained by linkage disequilibrium with the DR52-associated DRB1 alleles. It must be noted that the DR8 haplotype, which does not possess the DRB3 gene, also showed a significant increase in sarcoidosis. These results suggest that the HLA-alleles responsible for the susceptibility to sarcoidosis are located at the HLA-DRB1 locus rather than the HLA-DRB3, -DQA1 and -DQB1 loci. In contrast, DRB1*1302 may confer resistance to the disease.     

TWELVE HLA-DR6-RELATED DRB1 ALLELES AND ASSOCIATED DR,DQ HAPLOTYPES IN TRADITIONAL AUSTRALIANS AND OTHER POPULATIONS OF ASIA-OCEANIA

The relative distributions of 12 HLA-DR6-related HLA-DRB1 alleles in indigenous populations of Australia, Melanesia, Polynesia, Micronesia, and northern and southern China have been determined by analysis of nucleotide sequence polymorphisms in 364 examples of HLA-DR6 positive chromosomes. Oligonucleotide hybridizations of polymerase chain reaction products of HLA-DQA1, DQB1, DRB1 and DRB3 genes generated 24 HLA-DR6-related haplotypes. The study aimed to determine the regional distribution of DR DQ haplotypes associated with three novel HLA-DR6 alleles, namely DRB1*1408, 1409, and 1410, known to occur in Australian Aborigines, to gain further insights into the molecular phylogeny of these alleles. DRB1*1408 was the most common HLA-DR6 subtype in Oceania, although it was not detected in Chinese. In Australian Aborigines and Papua New Guinean highlanders, DRB1*1408 was associated with DRB3*0202, while in Polynesians and Micronesians it was associated with DRB3*0101. The different haplotype arrangements, together with the near absence of DRB1*1408 in coastal Melanesians, suggest the possibility that two independent mutations have generated DRB1*1408 in Australia and Oceania. DRB1*1409 and 1410 alleles were confined to Australian Aborigines, while DRB1*1407 was found exclusively in Melanesians; DRB1*1401 was the only HLA-DR6 allele represented in all study populations. The population-specific HLA-DR6 alleles and haplotypes have important implications for unrelated bonemarrow donor registries in Australia and Oceania.     

The role of HLA molecules in susceptibility to chronic rheumatic heart disease

Only a small fraction of the streptococcal pharyngitis progress to rheumatic carditis, which implies that environmental, host and microbial factors interact to cause an aberrant immune response against the antigens of the microorganism that cross-react with cardiac tissues. Although there are numerous studies and a general consensus on the relation between human leucocyte antigen (HLA) class II antigens and rheumatic heart disease (RHD), the details and the culprit antigens are still controversial. The study was undertaken to examine 100 patients with chronic RHD and 100 controls for HLA class I and class II antigens for differences in prevalence. All samples were typed at the HLA-DRB1/3/4/5 and DQB1 loci by the sequence-specific primer (PCR-SSP) method at low resolution. For HLA class I antigens, HLA-B13 frequency was marginally increased in patients with RHD compared to controls without reaching statistical significance. For class II antigens, RHD patients had higher frequencies for HLA-DRB1*01 (RHD 24%, controls 10%), DRB1*04 (RHD 35%, controls 26%), DRB1*07 (RHD 18%, controls 11%) and HLA-DQB1*02 (RHD 32%, controls 17%) without reaching statistical significance, and significantly lower frequencies for DRB1*13 (Pc < 0.003, OR: 5.69), DRB5* (Pc < 0.003, OR: 33) and DRB3* (Pc = 0.03, OR: 2.66) compared to controls. It was concluded that host, microbial and environmental factors collude to create acute rheumatic fever (RF) and chronic rheumatic valve disease. The HLA-DRB1*13, DRB5* and DRB3* were protective against the development of rheumatic valve damage.     

DNA typing for HLA-DR, and -DP alleles in a Chinese population using the polymerase chain reaction (PCR) and oligonucleotide probes

We have determined alleles of HLA-DRB1, DRB3, DRB5, DQA1, DQB1, and DPB1 loci in 91 unrelated healthy individuals from North China. Group-specific PCR primers were employed for the analysis of subsets of DR1, DR2, DR4, DRw52, and DPB. With allele-specific probes, 22 DRB1, 8 DQA1, 13 DQB1, and 12 DPB1 alleles were found in this panel. Allele frequencies showed that 25.3% of the subjects had DR7 and 26.4% had DR9, only 5.5% had DRB1*0301 (DRw17). In the DR4 group, DRB1*0405 (Dw15, 8.8%) and 0406 (KT2, 9.9%) were the most prevalent alleles. DRB1*0404 (Dw14.1), 0407 (Dw13.2) and 0408 (Dw14.2) were absent and the other alleles of the DR4 group were rare. The most common DRw6 subset was DRB1*1401 (8.8%). DRB1*0802 and 0803 were present (2.2%, 6.6%), and DRB1*0801 was not found. Associations with DQA1 and DQB1 were generally similar to those found in other populations. DPB1*0501 was the most frequent (60.2%) allele at the DPB1 locus. Overall our study shows that the distribution of class II alleles in a population from Mainland China is quite different from other ethnic groups. The high frequency of the KT2 subset of DR4. (DRB1*0406) and of DPB1*0501 are the most striking features found. A new type of DR4 was determined in one subject. It was like DR4-Dw15 (DRB1*0405) but, according to our hybridization patterns, it encoded valine instead of glycine in position 86. It is now called DRB1*0410.     

Twelve HLA-DR6-related DRB1 alleles and associated DR, DQ haplotypes in traditional Australians and other populations of Asia-Oceania.

The relative distributions of 12 HLA-DR6-related HLA-DRB1 alleles in indigenous populations of Australia, Melanesia, Polynesia, Micronesia, and northern and southern China have been determined by analysis of nucleotide sequence polymorphisms in 364 examples of HLA-DR6 positive chromosomes. Oligonucleotide hybridizations of polymerase chain reaction products of HLA-DQA1, DQB1, DRB1 and DRB3 genes generated 24 HLA-DR6-related haplotypes. The study aimed to determine the regional distribution of DR,DQ haplotypes associated with three novel HLA-DR6 alleles, namely DRB1*1408, 1409, and 1410, known to occur in Australian Aborigines, to gain further insights into the molecular phylogeny of these alleles. DRB1*1408 was the most common HLA-DR6 subtype in Oceania, although it was not detected in Chinese. In Australian Aborigines and Papua New Guinean highlanders, DRB1*1408 was associated with DRB3*0202, while in Polynesians and Micronesians it was associated with DRB3*0101. The different haplotype arrangements, together with the near absence of DRB1*1408 in coastal Melanesians, suggest the possibility that two independent mutations have generated DRB1*1408 in Australia and Oceania. DRB1*1409 and 1410 alleles were confined to Australian Aborigines, while DRB1*1407 was found exclusively in Melanesians; DRB1*1401 was the only HLA-DR6 allele represented in all study populations. The population-specific HLA-DR6 alleles and haplotypes have important implications for unrelated bone-marrow donor registries in Australia and Oceania.     

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.     

New revelations in susceptibility to autoimmune thyroiditis by the use of H2 and HLA class II transgenic models

H2 and HLA transgenes were utilized to clarify the role of class II genes in susceptibility to experimental autoimmune thyroiditis (EAT), a model for Hashimoto's thyroiditis (HT). Susceptibility was transferred by H2 class II transgenes to a resistant haplotype and by HLA-DRA/DRB1*0301 (DR3) transgene into class II-negative Ab0 mice. Mice with a HLA-DRB1*1502 (DR2) transgene remain resistant to mouse thyroglobulin (mTg)-induced EAT, illustrating the role of HLA-DRB1 polymorphism. A role for HLA-DQ polymorphism was shown with hTg-induced EAT in HLA-DQ*0301/DQB1*0302 (DQ8), but not HLA-DQ*0103/DQB1*0601 (DQ6), transgenic mice. Yet, both DQ8+ and DQ6+ mice were unresponsive to mTg. Single transgenes obviate the problems from DR/DQ linkage disequilibrium and may distinguish the degree of susceptibility and the response to shared or specific epitopes. The introduction of conserved Eak transgene into Ab0 mice reveals a new role for H2E molecules in EAT. Without H2A molecules, EalphaEbetab molecules and T cells respond to hTg or pTg with severe thyroiditis, but not to mTg, thus distinguishing self from nonself. However, IAb genes in resistant mice ameliorate Eak transgene-mediated thyroiditis, similar to the effect of Eak transgene on IAs-mediated EAT. Studies in HLA DQ/DR double transgenic mice simulating human haplotypes could reveal HLA class II gene interactions in HT.     

HLA-A, -B, -C, -DRB1 and -DQB1 alleles and haplotypes in the Kinh population in Vietnam

Allele and haplotype frequencies of the human leukocyte antigens (HLA) were studied in the Kinh Vietnamese population. We analyzed 170 unrelated healthy individuals. DNA-based HLA typing was performed using a microsphere-based array genotyping platform with sequence-specific oligonucleotide probes to distinguish HLA-A, -B, -C, -DRB1 and -DQB1 alleles. A total of 21 HLA-A, 37 HLA-B, 18 HLA-C, 25 HLA-DRB1, and 14 HLA-DQB1 alleles were identified. HLA-A*1101, A*2402, A*3303, B*1502, B*4601, Cw*0102, Cw*0702, Cw*0801, DRB1*1202, DQB1*0301, DQB1*0303, and DQB1*0501 were found with frequencies higher than 10%. Two representative haplotypes bearing two to five HLA loci were A*1101-B*1502 and A*3303-B*5801 for HLA-A-B; Cw*0801-B*1502 and Cw*0102-B*4601 for HLA-C-B; B*1502-DRB1*1202 and B*4601-DRB1*0901 for HLA-B-DRB1; DRB1*1202-DQB1*0301 and DRB1*0901-DQB1*0303 for HLA-DRB1-DQB1; A*1101-Cw*0801-B*1502 and A*3303-Cw*0302-B*5801 for HLA-A-C-B; A*1101-B*1502-DRB1*1202 and A*2901-B*0705-DRB1*1001 for HLA-A-B-DRB1, A*1101-Cw*0801-B*1502-DRB1*1202-DQB1*0301 and A*2901-Cw*1505-B*0705-DRB1*1001-DQB1*0501 for HLA-A-C-B-DRB1-DQB1. Allele distribution and haplotype analysis demonstrated that the Vietnamese population shares HLA patterns with southern Chinese, Thai, Javanese and Micronesians, while it also retains unique characteristics.     

Polymorphisms of HLA genes in Western Javanese (Indonesia): close affinities to Southeast Asian populations

Identification of human leukocyte antigen (HLA) antigens that are known as the highest polymorphic genes has become a valuable tool for tissue transplantation, platelet transfusion, disease susceptibility or resistance, and forensic and anthropological studies. In the present study, the allele and haplotype frequencies of HLA-A, HLA-B, and HLA-DRB1 were studied in 237 unrelated healthy Western Javanese (Indonesia) by the high-resolution polymerase chain reaction-Luminex method. A total of 18 A, 40 B, and 20 DRB1 alleles were identified. The most frequent HLA-A, -B, and -DRB1 alleles were HLA-A*2407 (21.6%), HLA-B*1502 (11.6%) and HLA-B*1513 (11.2%), and DRB1*1202 (37.8%), respectively. The most frequent two-locus haplotypes were HLA-A*2407-B*3505 (7%) and HLA-B*1513-DRB1*1202 (9.2%), and three-locus haplotypes were HLA-A*3401-B*1521-DRB1*150201 (4.6%), HLA-A*2407-B*3505-DRB1*1202 (4.3%), and HLA-A*330301-B*440302-DRB1*070101 (4.2%). HLA allele and haplotype frequencies in addition to phylogenetic tree and principal component analyses based on the four-digit sequence-level allele frequencies for HLA-A, HLA-B, and HLA-DRB1 showed that Western Javanese (Indonesia) was closest to Southeast Asian populations.     

HLA-DRB1, -DQA1, -DQB1 and DPB1 susceptibility alleles in Cameroonian type 1 diabetes patients and controls.

It is known that certain combinations of alleles within the human leucocyte antigen (HLA) complex are associated with susceptibility or resistance to type 1 diabetes. Variable associations of DR and DQ with type 1 diabetes are documented in Caucasians but rarely in African populations; however, the role of HLA-DP genes in type 1 diabetes remains uncertain. In order to investigate the HLA class II associations with type 1 diabetes in Cameroonians, we used sequence-specific oligonucleotide probing (SSOP) to identify DRB1, DQA1, DQB1 and DPB1 alleles in 10 unrelated C-peptide negative patients with type 1 diabetes and 90 controls from a homogeneous population of rural Cameroon. We found a significantly higher frequency of the alleles DRB1*03 (chi2 = 17.9; P = 0.001), DRB1*1301 (chi2 = 37.4; P < 0.0001), DQA1*0301 (chi2 = 18.5; P = 0.001) and DQB1*0201 (chi2 = 37.4; P < 0.001) in diabetes patients compared to the control group. The most frequent alleles in the control population were DQA1*01, DQB1*0602 and DRB1*15. The DRB1*04 allele was not significantly associated with type I diabetes in our study population. We observed no significant difference between patients and controls in DPB1 allele frequency. In conclusion, the data in Cameroonian diabetes patients suggest the existence of HLA class II predisposing and specific protective markers, but do not support previous reports of a primary association between HLA-DP polymorphism and development of type I diabetes.     

HLA-DRB1 and HLA-DQB1 polymorphisms in Pacific Islands populations

Allele frequency distributions of the HLA-DRB1 and HLA-DQB1 genes were investigated in four Pacific Islands populations from the Cook Islands, Samoa, Tokelau and Tonga. Limited diversity was observed for both the HLA-DRB1 and HLA-DQB1 loci. Five HLA-DRB1 alleles were observed to be the most frequent amongst all the studied Pacific Islands populations. They were: HLA-DRB1*0403, HLA-DRB1*08032, HLA-DRB1*09012, HLA-DRB1*11011 and HLA-DRB1*1201. Cook Islanders had the largest number of low frequency DRB1 alleles followed by Samoans, Tokelauans and Tongans, most of which may be attributed to reported non-Polynesian admixture. The most frequently observed DQB1 alleles in the four studied Pacific Islands populations were those of the DQ3 subgroup of alleles HLA-DQB1*03011, HLA-DQB1*0302 and HLA-DQB1*03032 as well as HLA-DQB1*05031 and HLA-DQB1*06011. Cook Islanders had the highest number of rare HLA-DQB1 alleles, the distibution being similar to that of the HLA-DRB1 allele. While, in general, the values of homozygosity for DRB1 and DQB1 were observed to be lower then expected under neutrality, a statistical significance was observed in Tongans, Samoans and Tokelauans for the DQB1 locus and in Tongans for the DRB1 locus. Differences were observed between allele frequency distributions for Tokelauans compared to the other three populations. This was also demonstrated by principal component analysis of DRB1 and DQB1 allele frequencies, which separated the Tokelauan population from Cook Islanders, Tongans and Samoans. Tongans and Samoans were separate from the other Polynesian populations in the phylogenetic trees. Observed allele and haplotype frequencies were found to be in agreement with previously published HLA-DRB and HLA-DQB Polynesian data.