HLA genotyping of colorectal carcinoma in the Chinese population.

The HLA-DR genotypes of 61 primary colorectal carcinomas obtained from patients of Chinese origin were determined by using DNA-RFLP. No increase or decrease of a particular HLA genotype could be ascertained with the disease, although we detected an antigen frequency of 29.5% for the serologically ill-defined DR"X3" specificity. We identified and sequenced HLA-DRB1 and DRB3 genes from the DR"X3" haplotype. The DR"X3" DRB1 gene was found to be identical to DRB1*1201 (DR5[w12]). A unique observation is its unusual linkage with DRB3*0101 (DRw52a) or DRB3*0301 (DRw52c) instead of the usual linkage with DRB3*0201/2 (DRw52b). These associations are rare in whites and blacks.     

HLA polymorphism in a Mataco South American Indian tribe: Serology of class I and II antigens: Molecular analysis of class II polymorphic variants

In the present study, HLA-A, B, C, DR, DQ, and DP loci were analyzed in a group of Mataco Amerindians of Argentina. Using reagents from the 11th International Histocompatibility Workshop (11th IHW), class I specifities such as Bw70, Bw75, and Bw48 were found in this population, other than the HLA determinants commonly described in South American Indians. The class II antigens found were DR4, DRw14, and DRw8 at the DR locus, and DQw4 and DQw7 at the DQ locus. The analysis of DRB1-DR4 related alleles, performed by PCR amplification and oligonucleotide probe hybridization, showed the presence of DRB1*0403, *0404, *0405, and *0411 in individuals from this ethnic group. By the analysis of DRB1-DRw14 related alleles, two variants were found: DRB1*1402 and DRB1*1406, the latter provisionally called DRB1 14.6 in 11th IHW. The DRw8-related allele present was DRB1*0802. The analysis of DRB3 gene revealed only the presence of DRB3*0101 allele in DRw14 individuals. DPB1 locus was also analyzed in unrelated individuals of the same population. Only five DPB1 alleles were found: DPB1*0201, *0301, *0402, *0501, and *1301 over the 19 previously described in the literature. These findings emphasize the restricted HLA class I and II variation observed in this ethnic group as it has been previously shown in other American groups. Some particular haplotypes in this Mataco tribe are described in this work.     

Polymorphism of HLA-DRw52-associated DRB1 genes as defined by sequence-specific oligonucleotide probe hybridization and sequencing

We have used group-specific DNA amplification and sequence-specific oligonucleotide probe (SSOP) hybridization to study DRB1 sequence polymorphisms associated with DR3, DRw11(5), DRw12(5), DRw13(w6), DRw14(w6) and DRw8 alleles. Group-specific amplification of DRw52-associated DRB1 alleles was achieved using a 5' amplification primer designed to hybridize with a first hypervariable region (HVR) sequence common to all known alleles in this group, together with a 3' intron primer. Prospective SSOP typing of DR3, DRw11, DRw12, DRw13, DRw14 and DRw8 alleles was performed in 318 individuals, including 124 patients, 46 family members and 148 unrelated marrow donors. Among the 395 DRw52-associated DRB1 alleles tested in our study, a subtype corresponding to the previously defined alleles DRB1*0301-2 (DR3), DRB1*1101-4 (DR5), DRB1*1201-2 (DR5), DRB1*1301-5 (DRw6), DRB1*1401-2 and 1404 (DRw6), and DRB1*0801-4 (DRw8) could be assigned in all but 6 individuals (1.9%) tested. In addition to the 22 known alleles, we identified two new DRw6-associated alleles, DRB1*13.MW(1) and DRB1*14.GB(1). DRB1*13.MW typed serologically as DRw13 and was identical to DRB1*1301 except at codon 71 where AGG encodes arginine instead of GAG encoding glutamic acid. DRB1*14.GB represents a DRB1*1402 variant whose sequence at codon 86 encodes valine (GTG) instead of glycine (GGT). These results demonstrate that SSOP methods represent an efficient and precise approach for typing DRB1 alleles and for identifying potential novel variants previously unrecognized by conventional typing methods.     

HLA-A*11 and novel associations in Malays and Chinese with systemic lupus erythematosus

We investigated the association of the HLA genes in Malaysian patients with systemic lupus erythematosus (SLE) and their associations with the clinical manifestations in 160 SLE patients (99 Chinese and 61 Malays) and 107 healthy control individuals (58 Chinese and 49 Malays) were studied. Sequence specific primer amplification (PCR-SSP) phototyping techniques were used to analyse 25 HLA-A allele groups, 31 HLA-DR allele groups and 9 HLA-DQ allele groups. Appreciable increases in allele frequencies of HLA-A*11, DRB1*0701, DRB1*1601-1606, DRB5*01-02 and DQB1*05, and decrease in HLA-DRB1*1101-1121, 1411, DRB1*1201-3, DRB1*1301-22, DRB3*0101, 0201, 0202, 0203, 0301 and DQB1*0301, 1304 in SLE patients compared with healthy control individuals. However, after Bonferroni correction (p(c)<0.05) only HLA-A*1101, 1102, DRB5*01-02, DQB1*05, DRB1*1201-3, DRB3*0101, 0201, 0202, 0203, 0301 and DQB1*0301, 0304 remained significant. Allele frequencies of DRB1*0701 and DRB4*0101101, 0102, 0103, DQB1*05, DRB1*1301-22, DRB3*0101, 0201, 0202, 0203, 0301 and DQB1*0301, 0304 were significantly increased in Malay SLE patients compared with healthy control individuals. In contrast, Chinese SLE patients had increased allele frequencies of DRB1*1601-1606, DQB1*05, DRB1*1201-3, DRB3*0101, 0201, 0202, 0203, 0301, DRB3*0101, 0201, 0202, 0203, 0301 and DQB1*0301, 0304 compared with healthy control individuals. HLA-A*6801-02 and DRB1*1601-1606 frequencies appeared elevated in a subset of patients with serositis and DRB1* 0401-1122 frequency was elevated in those displaying neurologic disorder. However, unequivocal evidence of these associations would require investigation of substantially larger cohorts. On the whole, our findings suggest that HLA allele associations with SLE are race specific in Malays and Chinese.     

Sequence of a new DR12 allele with two silent mutations that affect PCR-SSP typing

A new HLA-DR12 allele has been identified in a European Caucasoid bone marrow donor. The DRB1*12012 allele differs from DRB1*12011 by two silent substitutions at codons 72 and 78, two polymorphic positions used for DNA subtyping of the DR12 serotype. The co-occurence of the two nucleotide changes is unique to the DR12 group and results in a new PCR-SSP typing pattern. The complete HLA type of the donor is A24, A68; B55, B61; Cw*01, Cw*0304; DRB1*12012, DRB1*1402; DRB3*0101, DRB3*0202; DQB1*0301. HLA-DRB1*12012 is a rare allele as it occurs in < 0.2% of DR12 donors.     

HLA antigens in Tlingit Indians with rheumatoid arthritis

HLA-DR4 has been described in association with rheumatoid arthritis (RA) in multiple populations. We have studied HLA antigens in Alaskan Tlingit Indians. HLA-DR4 was decreased in the RA group (n = 32) compared with controls (n = 62) (6% vs 21% p = 0.07). The predominant DR4 allele observed was DRB1*0403 (Dw13.1). The most striking observation in these studies was a marked predominance of the DRB1*1402 allele encoding Dw16 (DRw14). This allele was present in 91% of RA cases, but was also highly prevalent in controls (80%, OR = 2.4 p = 0.20). DRB1*1402 only was observed in 47% of cases and 31% of controls. The DRB3*0101 (DRw52), and the DQA*0501 and DQB*0301 alleles encoding a subset of DQw3 were associated with DRB1*1402 in cases and in controls. HLA-Bw62 was increased in RA cases (28%) compared with controls (8%) (OR = 4.5, p = 0.01, corrected p = ns).     

Increasing complexity of HLA-DR2 as detected by serology and oligonucleotide typing.

Serological and oligonucleotide typing was performed on a number of HLA-DR2-positive cells from different ethnic origin, including DR2 haplotypes with various DQ associations. Exons 2 of DRB1 and DRB5 of DR2-positive individuals were locus-specific amplified and hybridized with a number of different oligonucleotides capable of discriminating between the various Dw2, Dw12, Dw21, and Dw22 associated sequences. The linkage of DRB with DQA1 and DQB1 in these haplotypes was analyzed. Among the DR2- positive cells we could define 10 different DR DQ haplotypes by serology and 13 by oligonucleotide typing. The DR2.ES specificity is a serological DRw15 variant which could not be discriminated by oligonucleotide typing from a DRw15 DQw5 haplotype. The DR2.JA variant represents a unique DRB1*1602 DRB5*0101 haplotype. The DR1+2s haplotype consists of a DRB1 DQ region from a Dw1 and a DRB5 gene from a Dw2 haplotype. Its short DR2 serum pattern can be explained by the absence of a DR2 DRB1 gene product. DRB5*0101 sequences were found in association with DRB1*1501, *1502, *1602, and *0101 alleles. Since the DRB5 gene is capable of such different associations it is comparable to the DRB3 and DRB4 genes. This may have implications for the definition of the broad DR2 specificity which is predominantly encoded by the DRB5 gene product. New DR2 haplotypes included the following DQ combinations: DQw2-positive DQA1/B1*0301/0201 and DQw6-positive DQA1/B1*0102/0601 and *0102/0603 haplotypes.     

HLA-DRB1 and -DRB3 allele frequencies and haplotypic associations in Koreans

We have investigated the frequencies of human leukocyte antigen-DRB1 (HLA-DRB1) and -DRB3 alleles and DRB1-DRB3 haplotypic associations in 800 Koreans. DRB1 genotyping was done using polymerase chain reaction-sequence-specific oligonucleotide (PCR-SSO) and PCR-single strand conformation polymorphism (SSCP) methods. DRB3 genotyping was done on 447 samples carrying DRB3-associated DRB1 alleles (DRB1*03, *11, *12, *13, and *14) using PCR-SSCP method. The allele frequencies of DRB3*0101, DRB3*0202, and DRB3*0301 were 0.073, 0.136, and 0.120, respectively, and we found one case of a probable new allele (DRB3*01new, 0.001). DRB1-DRB3 haplotypes with frequency (HF) > 0.005 exhibited strong associations between DRB3*0101 and DRB1*1201, *1301, and *1403; between DRB3*0301 and DRB1*1202 and *1302; between DRB3*0202 and DRB1*0301, *1101, *1401, *1405, and *1406 alleles. Most of the DRB1 alleles with frequency > 0.005 were exclusively associated with particular DRB3 alleles with relative linkage disequilibrium values of 1.0, except for DRB1*1201, *1202 and *1301; the rare presence (HF < 0.005) of DRB3*0202 associations were observed for these DRB1 alleles. We also investigated and presented rare DRB1-DRB3 associations in additional 6000 Koreans. Comparison with other ethnic groups revealed that DRB1*0301 and *1301 related DRB1-DRB3 haplotypes vary among different populations, in that Koreans and other Asian populations show less diversity compared with Caucasoids or African Americans.     

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.     

HLA class II alleles associated with celiac disease susceptibility in a Southern European population

Susceptibility to celiac disease in Northern Europe is associated with the human leukocyte antigens (HLA) B8, DR3 and DQ2, which exist together on an extended haplotype. The strong predominance of this haplotype within the Northern European celiac populations, together with the linkage disequilibrium which occurs between these loci, does not allow identification of the gene(s) primarily associated with disease susceptibility. Studies from Southern Europe using both serology and examination of restriction fragment length polymorphisms (RFLP) have demonstrated associations with DR3, DR7 and DQ2, suggesting that the DQ locus is primarily involved. We investigated 43 celiac patients and 41 healthy controls from Rome, Italy, using sequence-specific oligonucleotide (SSO) probes, in conjunction with gene amplification by the polymerase chain reaction (PCR), to determine alleles at the DRB, DQA1, DQB1 and DPB1 loci: 19% of celiac patients possessed the alleles DRB1*0301 DRB3*0101, 33% DRB1*0301 DRB3*0201 and 33% of celiac patients were heterozygous for DRB1*1101-1201/DRB1*0701. The strongest association with celiac disease susceptibility was the combination of alleles DQA1*0501 DQB1*0201 (91% celiac patients vs. 12% controls; p = 0.000002). There was no additional susceptibility associated with alleles at the DPB locus. This study confirms the hypothesis that susceptibility is associated with a particular combination of DQ alleles and the ethnic variation in DR frequencies is secondary to linkage disequilibrium with these DQ alleles.     

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.     

Comprehensive typing of DR52 (DRB3)-associated DRB1 and DRB3 alleles by PCR-RFLP

Abstract: The DR52-associated DRB1 and DRB3 alleles were resolved by PCR-RFLP. Second exon was amplified using four primer pairs (groups 1–4) for DRB1 and a pair for DRB3 alleles. Except for three endonucleases, all others had either none or only one site for a specific amplified product. Group 1 primers amplify 10 DRB1 alleles (DRB1*0302, 1101, 1302, 1303, 1305, 1307, 1402, 1403, 1407 and 1409). All but one pair, DRB1*1402 from 1409, could be resolved using seven endonucleases (ApaI, SacII, FokI, AvaII, BsaAI, BsrBI and SfaNI). Group 2 consisted of four alleles (DRB1*1201, 1202, 1404 and 1411) that can be resolved along with co-amplified DRB1*0804 and 0806 using five endonucleases (AvaII, SacII, FokI, HaeII and RsaI). Group 3 primers amplify 15 DRB1 alleles (DRB1*0301, 0303, 1102, 1103, 1104, 1107, 1301, 1304, 1306, 1308, 1401, 1405, 1406, 1408 and 14-New), which can be resolved using nine enzymes (KpnI, AvaII, FokI, SacII, HaeII, BsrBI, SfaNI, DdeI and RsaI). BsrBI, a new endonuclease, can resolve DRB1*1301 from 1306 and the previously unresolved allele DRB1*1103 from 1104. DRB1*1410, co-amplified with DR4 group-specific primers, is resolved with PstI which cleaves all DR4 alleles but not DRB1*1410. All four DRB3 alleles (DRB3*0101, 0201, 0202 and 0301) and their heterozygotes are resolved using two endonucleases, RsaI and HphI. Thirty-four DR52-associated alleles and their heterozygotes can be unambiguously resolved, except for DRB1*1402 from 1409. Thus, PCR-RFLP remains an effective method for high-resolution HLA-DR typing. Furthermore, PCR-RFLP can complement the evolving PCR-SSP method for allele-specific typing using a minimal number of restriction endonucleases.     

Additional complexity within the HLA-D region: sequence analysis of two new DRw13-DQw7 haplotypes.

HLA-DRB1 is by far the most polymorphic locus within the HLA-D region with now well over 40 alleles. Nearly one fourth of these alleles are subtypes of DRw6, and these are in most cases undetectable by routine typing procedures. In this paper we present the molecular characterization of two new Caucasian DRw13-DQw7 haplotypes by DNA sequencing of the polymorphic first domain exons of DRB1 and DRB3 loci. The first haplotype, DRB1*1301-DRB3*0101-DQB1*0301, has arisen by a recombination between locus DRB1 from a DRw13-DQw6 haplotype and DQA1 from a DR4-DQw7 haplotype, as determined by DNA sequencing, DQ oligotyping, and restriction fragment length polymorphism typing. The second haplotype, DRB1*1305-DQB1*0301, is characterized by the novel DRB1*1305 allele differing from DRB1*1301 by three amino acids. It probably arose by a gene conversion event between a DRw13-DQw6 allele and DRB1*1101. This allele represents a DRw11/DRw13 hybrid DR molecule with a DRw13 serological epitope in the second hypervariable region and a Dw5 cellular epitope in the third hypervariable region. As determined by sequencing of locus DRB3, this allele is associated with DRw52b. Our molecular analysis of the complex HLA-DRw13 group now allows unambiguous DNA typing of all five DRw13 alleles with seven oligonucleotides, a significant improvement in the context of organ transplantation.     

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-DRB and -DQB1 polymorphism in the Macedonian population

HLA-DRB1, DRB3/4/5 and DQB1 polymorphism has been studied in a population of 80 unrelated healthy Macedonians using molecular methods. Twenty-five different DRB1 alleles were identified of which DRB1*1104, *1501, *1601, and *1101 were found most frequently. Among the 15 identified DQB1 alleles, two were predominant: DQB1*0301 and *0502. The most frequent three-locus haplotypes were DRB1*1104-DRB3*02-DQB1*0301 (18%/), DRB1*1101-DRB3*02-DQB1*0301 (9%) and DRB1*1601-DRB5*02-DQB1*0502 (10%). Polymorphism for DRB1*04, *13 and *15 haplotypes was extensive. Eleven different DR2-related haplotypes were found, some of which were unusual for European populations: DRB1*1501-DRB5*0102-DQB1*0502, DRB1*1501-DRB5*02-DQB1*0502, DRB1*1501-DRB5*0102-DQB1*0601.     

Polymorphism of DR52-associated haplotypes in a Croatian population

We investigated DR52 haplotype polymorphism in a population of 78 Croatian families with at least one parent and one offspring positive for a DR52-associated allele, using the PCR–SSOP method. The haplotypes DRB1*0301-DQA1*0501-DQB1*0201, DRB1*11-DQA1*0501-DQB1*0301 and DRB1*1201-DQA1*0501-DQB1*0301 seem to be conserved haplotypes in this Croatian population, while DRB1*13 haplotypes showed high diversity. Among 10 different DRB1*13 haplotypes, four consist of common alleles, while six have an unusual combination of DRB1-DQA1-DQB1 alleles. Three haplotypes (DRB1*1301-DQA1*0103-DQB1*0503, DRB1*1302-DQA1*0102-DQB1*0502 and DRB1*1303-DQA1*0102-*DQB1*0502) have not been reported. These results on DR52-associated haplotype polymorphisms in a Croatian population must be taken into consideration in organ transplantation, especially when searching for unrelated bone marrow donors.     

Rapid DNA typing utilizing immobilized oligonucleotide probe and a nonradioactive detection system. Application to HLA-DR typing of the Japanese population.

We established a rapid and simple method of HLA-DR genotyping, and applied it for analysis of the Japanese population. Our method includes rapid preparation of DNA samples from buccal mucosa, incorporation of biotin-dATP into DRB genes during amplification by the polymerase chain reaction, hybridization with sequence-specific oligonucleotide (SSO) probes immobilized on nylon membranes via poly (dT) tails, and detection of the hybridization signal as chemiluminescence. We carried out DR typing of 30 Japanese donors using 20 different immobilized SSO probes, and obtained unambiguous typing signals showing perfect correlation with their serologic DR types. The genotyping also enabled us to identify several DR types unique to the Japanese population, such as DRw12b (DRB1*1202), DRw14c (DRB1*1405), and serology blank type, DR'JX6' (DRB1*1403). The method presented here would be suitable for routine DR typing in tissue-typing laboratories.     

Polymorphism of DR52-associated haplotypes in a Croatian population.

We investigated DR52 haplotype polymorphism in a population of 78 Croatian families with at least one parent and one offspring positive for a DR52-associated allele, using the PCR-SSOP method. The haplotypes DRB1*0301-DQA1*0501-DQB1*0201, DRB1*11-DQA1*0501-DQB1*0301 and DRB1*1201-DQA1*0501-DQB1*0301 seem to be conserved haplotypes in this Croatian population, while DRB1*13 haplotypes showed high diversity. Among 10 different DRB1*13 haplotypes, four consist of common alleles, while six have an unusual combination of DRB1-DQA1-DQB1 alleles. Three haplotypes (DRB1*1301-DQA1*0103-DQB1*0503, DRB1*1302-DQA1*0102-DQB1*0502 and DRB1*1303-DQA1*0102-*DQB1*0502) have not been reported. These results on DR52-associated haplotype polymorphisms in a Croatian population must be taken into consideration in organ transplantation, especially when searching for unrelated bone marrow donors.     

HLA—DR基因多态性与广东汉族泛发型白癜风患者的相关性研究

目的研究广东籍汉族泛发型白癜风患者与HIA—DR的相关性。方法采用聚合酶链反应一序列特异性引物（PCR．SSP）技术，对30例广东籍汉族泛发型白癜风患者和30例健康对照者静脉血样本HLA-DR等位基因多态性进行研究。结果泛发型白癜风患者DRB1^＊0701等位基因频率显著升高（RR=5．216，PC〈0．05），DRw52（DRB3^＊0101／02DRB3^＊0201DRB3^＊0301）、DRw53（DRB4^＊0101／03／05）和DRw51（DRB5^＊0101／02DRB5^＊0202）基因频率明显低于正常组，以上三者两组间比较均有显著性差异（PC〈0．05）。结论HIJA—DRB1^＊0701等位基因可能与广东籍汉族泛发型白癜风的发病有关，而DRw52（DRB3^＊0101／02DRB3^＊0201DRB3^＊0301）、DRw53（DRB4^＊0101／03／05）和DRw51（DRB5^＊0101／02DRB5^＊0202）对泛发型白癜风发病可能有一定保护作用。     

A novel DRB1*13 allele (DRB1*1327) on a DR17, DQ2 haplotype with a DRB1*0301 sequence motif in the 2nd hyperpolymorphic region

In a sample from a Netherlands Caucasian, we found a new DRB1*13 allele ( DRB1*1327 ). The nucleotide sequence of the second exon of the novel allele was identical to DRB1*1301 except for a single productive base substitution changing codon 26 from TTC to TAC, encoding phenylalanine and tyrosine, respectively. The new allele shares sequence with DRB1*03011 from codons 5 to 66. The haplotype carrying the new allele was, from known linkage disequilibria, deduced to be DRB1*1327, DRB3*0101, DQA1*05011, DQB1*0201 , i.e. similar to the DR17, DQ2 haplotype, which suggests that the DRB1*1327 allele has arisen by a double recombination event between a DR13 donor haplotype and a DR17, DQ2 recipient haplotype.