DQB1 Haplotypes Research Articles

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

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

Clear and independent associations of several HLA-DRB1 alleles with differential antibody responses to hepatitis B vaccination in youth.

To confirm and refine associations of human leukocyte antigen (HLA) genotypes with variable antibody (Ab) responses to hepatitis B vaccination, we have analyzed 255 HIV-1 seropositive (HIV+) youth and 80 HIV-1 seronegatives (HIV−) enrolled into prospective studies. In univariate analyses that focused on HLA-DRB1, -DQA1, and -DQB1 alleles and haplotypes, the DRB1*03 allele group and DRB1*0701 were negatively associated with the responder phenotype (serum Ab concentration ≥ 10 mIU/mL) (P = 0.026 and 0.043, respectively). Collectively, DRB1*03 and DRB1*0701 were found in 42 (53.8%) out of 78 non-responders (serum Ab <10 mIU/mL), 65 (40.6%) out of 160 medium responders (serum Ab 10–1,000 mIU/mL), and 27 (27.8%) out of 97 high responders (serum Ab >1,000 mIU/mL) (P < 0.001 for trend). Meanwhile, DRB1*08 was positively associated with the responder phenotype (P = 0.010), mostly due to DRB1*0804 (P = 0.008). These immunogenetic relationships were all independent of non-genetic factors, including HIV-1 infection status and immunodeficiency. Alternative analyses confined to HIV+ youth or Hispanic youth led to similar findings. In contrast, analyses of more than 80 non-coding, single nucleotide polymorphisms within and beyond the three HLA class II genes revealed no clear associations. Overall, several HLA-DRB1 alleles were major predictors of differential Ab responses to hepatitis B vaccination in youth, suggesting that T-helper cell-dependent pathways mediated through HLA class II antigen presentation are critical to effective immune response to recombinant vaccines.Electronic supplementary materialThe online version of this article (doi:10.1007/s00439-009-0720-z) contains supplementary material, which is available to authorized users.

HLA class II alleles in patients with multiple sclerosis in the Biscay province (Basque Country, Spain)

Genetic susceptibility to multiple sclerosis (MS) is associated with genes of the major histocompatibility complex, particularly with the HLA DRB1*1501-DQA1*0102-DQB1*0602 haplotype in Caucasians. To investigate the association of DRB1, DQA1 and DQB1 alleles and haplotypes with MS in Biscay, Basque Country, northern Spain, we examined 197 patients and 200 regionally matched controls. High resolution HLA class II typing was performed by polymerase chain reaction followed by sequence-specific oligonucleotide probe hybridization. Several alleles were overrepresented in MS patients compared with those of controls: DRB1*0402, DRB1*1303, DRB1*1501, DQA1*0102, DQB1*0301, and DQB1*0602. DQB1*0602 was the only potentially predisposing allele for MS that withstood Bonferroni correction and maintained the association in a logistic regression model. On the other hand, several alleles showed lower frequencies in the MS group: DRB1*0101, DQA1*0101, DQB1*0303, and DQB1*0501, but only DRB1*0101 and DQB1*0303 maintained a negative association with the disease in the regression analysis. Three haplotypes were identified as potentially predisposing for MS in our population: DRB1*1501-DQA1*0102-DQB1*0602, DRB1*0402-DQA1*0301-DQB1*0302, and HLA-DRB1*013-DQA1*05-DQB1*0301. Additionally, three haplotypes associated with a lower risk for MS were identified, exhibiting DRB1*0101-DQA1*0101-DQB1*0501 the strongest negative association with MS [12% in controls vs. 3.8% in MS, Pc = 0.00047, OR = 0.290 (95% CI = 0.160–0.528)], and suggesting, therefore, a putative protective role for this haplotype in the population under study.

Haplotype‐based search for SNPs associated with differential type 1 diabetes risk among chromosomes carrying a specific HLA DRB1–DQA1–DQB1 haplotype

The aim of this study was to test chromosomes carrying the same DRB1-DQA1-DQB1 haplotype for single nucleotide polymorphisms (SNPs) in the major histocompatibility complex (MHC) that might mark subgroups of the haplotype with different risks for type 1 diabetes (T1D). Chromosomes from T1D children, their parents and non-diabetic siblings in families of the Type 1 Diabetes Genetics Consortium (T1DGC) were analysed by two haplotype-based methods: (i) logistic regression analysis restricted to phased chromosomes carrying the same DRB1-DQA1-DQB1 haplotype but differentiated by the two alleles at MHC SNPs, which were individually tested for association with T1D and (ii) homozygous parent transmission disequilibrium test (TDT) for biased transmission of a SNP allele to diabetic children from parents who are heterozygous at the SNP but homozygous for the specific DRB1-DQA1-DQB1 haplotype being evaluated. A number of SNPs gave nominally significant (p < 0.05) evidence of marking two subsets of the 301-501-201 haplotype that might differ with respect to their diabetogenic potency. However, none of the SNPs achieved experiment-wide significance and hence may be false-positive associations. We discuss limitations and possible deficiencies of our study suggesting further work that might yield more robust SNP associations marking two subgroups of a DRB1-DQA1-DQB1 haplotype with different T1D risks.

Association of HLA class II alleles with childhood asthma and Total IgE levels.

Asthma is a complex and multifactorial disorder. Several studies have reported association between different HLA- DQB1 and HLA- DRB1 alleles and allergic asthma. The aim of the present study was to investigate the association of HLA-class II alleles and haplotypes, with total serum IgE and the results of the skin prick test in Iranian children with allergic asthma. A total of 112 patients with allergic asthma symptoms (75 males and 37 females) were selected randomly from the pediatric hospital. In some patients total serum IgE and prick test were determined. Data of this study shows that HLA-DRB1*12 significantly increased in asthmatic patients (4.5% vs. 0%, P-value=0.04). HLA-DQB1*0603 and 0604 alleles were significantly higher in asthmatics than those in normal controls (10% vs. 0%, P-value= 0.0001; and 9.3% vs. 3.7%, P-value= 0.04, respectively). The statistical significance was relinquished after p value correction for all alleles except for HLA-DQB1*0602 (Pc=0.03) and HLA-DQB1*0603 (Pc=0.0015). Conversely, HLA-DQB1*0501 and 0602 were decreased in asthmatics compared to normal controls (7.5% vs. 13.5%, P-value= 0.05; and 4% vs. 12.5%, P-value= 0.002, respectively). The mean of total IgE in patients was 483 IU, and it was significantly high about 1140 IU in asthmatic patients with positive skin prick test to house dust. The most frequent alleles in asthmatic patients with the total IgE>200 IU/mL were HLA-DRB1*11and 1401, HLA-DQA1*0505, HLA-DQB1*0301 and in patients with total IgE<200 IU/mL were HLA-DRB1*0301, 07 and 1301, HLADQA1*0201 and 0301, HLA-DQB1*0201. These data suggests that HLA-DRB1, DQA1 & DQB1 alleles and haplotypes might be implicated in susceptibility to allergy and asthma and serum IgE production. As asthma and atopy are multifactorial disorders, probably HLA genes are involved in the regulation of immune specific responses to common allergen.

From Type 1, through LADA, to Type 2 Diabetes: A Continuous Spectrum?

This study aims to explore whether diabetes mellitus from T1DM, through LADA, to T2DM presents a continuous spectrum in terms of HLA-DQ genetic background. We recruited 223 patients with autoimmune T1DM, 215 with LADA, 206 with T2DM, and 228 nondiabetic controls, and then defined their HLA-DQA1 and -DQB1 genotypes and haplotypes. T1DM patients were divided into two groups depending on age of onset of disease: juvenile-onset (JO; before the age of 20) and adult-onset (AO; after the age of 20). LADA patients were sorted according to the GADA titer: the LADA1 group had titers higher than 175 U/mL, whereas the LADA2 group had lower titers. The susceptible haplotypes of T1DM were DQA1*03-DQB1*0303, DQA1*03-DQB1*0401, and DQA1*05-DQB1*0201. The protective haplotype was DQA1*0102-DQB1*0602. The frequency of DQA1*03-DQB1*0303 in JO, AO, LADA1, LADA2, T2DM, and control groups were 38.2%, 34.2%, 25.3%, 18.9%, 17.5%, and 16.5%, respectively. The frequencies of DQA1*05-DQB1*0201 were 21.2%, 15.0%, 12.7%, 4.6%, 3.6% and 3.3%; the frequencies of DQA1*03-DQB1*0401 were 11.3%, 9.4%, 11.3%, 5.4%, 4.4% and 3.3%; and the frequencies of DQA1*0102-DQB1*0602 were 1.4%, 1.7%, 0.7%, 4.6%, 7.0%, and 5.3%. The linear-by-linear association showed that the frequency of DQA1*03-DQB1*0303, DQA1*05-DQB1*0201, and DQA1*03-DQB1*0401 presented a decremental tendency in JO, AO, LADA1, LADA2, T2DM, and control groups. The preliminary data demonstrated that the susceptible haplotypes of the HLA-DQ gene present a continuous spectrum from typical T1DM, through LADA, to T2DM, which deserves further investigation.

Influence of Common and Specific HLA-DRB1/DQB1 Haplotypes on Genetic Susceptibilities of Three Distinct Arab Populations to Type 1 Diabetes

The contribution of HLA DRB-DQB to type 1 diabetes (T1D) in Bahrainis, Lebanese, and Tunisians was investigated. DRB1*030101-DQB1*0201 was a locus that conferred susceptibility in three populations, while DRB1*040101-DQB1*0302 was a locus that conferred susceptibility only in Tunisians and Bahrainis. The DRB1*100101-DQB1*050101 (Bahrainis) and DRB1*150101-DQB1*060101 (Lebanese) loci were largely protective. The contribution of HLA to T1D must be evaluated with regard to ethnic background.

84-P: HLA-A, B, DRB1 and DQB1 allele and haplotype diversity in two Mexican Mestizo groups of different areas: Chiapas and Veracruz

84-P: HLA-A, B, DRB1 and DQB1 allele and haplotype diversity in two Mexican Mestizo groups of different areas: Chiapas and Veracruz

Association of HLA-DQA1 and DQB1 alleles with keloids in Chinese Hans

Some studies have suggested that human HLA status might potentiate development of keloids phenotype, and exists ethnic differences. No report has been published about HLA-DQA1 and DQB1 alleles associated with keloids in Chinese Hans. To investigate whether HLA-DQA1 and DQB1 alleles are associated with genetic susceptibility to keloids in Chinese Hans. Polymerase chain reaction-sequence-specific primer (PCR-SSP) method was used to analyze the distribution of HLA-DQA1 and DQB1 alleles among 192 patients with keloids and 273 healthy controls in Chinese Hans. (1) The frequencies of HLA-DQA1*0104, DQB1*0501 and DQB1*0503 (OR = 2.13, P(c) = 0.0063; OR = 14.42, P(c) < 10(-7) and OR = 6.09, P(c) < 10(-7), respectively) were significantly higher, while the frequencies of DQA1*0501, DQB1*0201 and DQB1*0402 (OR = 0.46, P(c) = 0.0099; OR = 0.24, P(c) < 10(-4) and OR = 0.10, P(c)=0.0054, respectively) were lower in patients than in controls. (2) In this study significant susceptibility haplotypes to keloids were DQA1*0104-DQB1*0501 and DQA1*0104-DQB1*0503. (3) HLA-DQB1*0501 and DQB1*0503 were positively associated with all subgroups of keloid patients. However, the DQA1*0104 (OR = 2.51, P(c) = 0.0009; OR = 2.22, P(c) = 0.0090 and OR = 2.20, P(c) = 0.0117, respectively) was only prevalent in keloid patients with single site, moderate severity and negative family history. (4) HLA-DQB1*0201 (OR = 0.27, P(c) = 0.0018 and OR = 0.27, P(c) = 0.0012, respectively) and DQB1*0402 (OR = 0.07, P(c) = 0.0270 and OR = 0.07, P(c) = 0.0306, respectively) were negatively associated with moderate severity and negative family history in keloids, moreover, HLA-DQB1*0201 (OR = 0.23, P(c) = 0.0003) and DQA1*0501 (OR = 0.43, P(c) = 0.0234) were less prevalent in patients with single site. This study demonstrated the positive association of HLA-DQA1 and DQB1 alleles and haplotypes with keloids.

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.

Islet autoantibodies are associated with HLA‐DQ genotypes in Han Chinese patients with type 1 diabetes and their relatives

The objective of this study was to explore the relationship between islet autoantibodies of glutamic acid decarboxylase (GADA), islet antigen-2A (IA-2A), insulin autoantibody (IAA), and human leukocyte antigen (HLA)-DQ genotypes in type 1 diabetes (T1D) patients and their first-degree relatives (FDRs). Cross-sectional and case-control study. Four hundred and ninety-five T1D patients, 419 FDRs, and 376 control subjects in Han Chinese populations were recruited and tested for GADA and IA-2A, while 71 cases, all FDRs and 300 controls were tested for IAA. The 338 T1D patients (including 187 antibody-positive and 151 antibody-negative patients), 173 FDRs and 278 controls were genotyped for HLA-DQ with polymerase chain reaction sequencing-based method. Compared with the control, the frequency of DQA1*03-DQB1*0303, DQA1*05-DQB1*0201, and DQA1*03-DQB1*0401 haplotypes was higher (P < 0.05-0.01) but DQA1*0102-DQB1*0602 haplotype was lower (P < 0.01) in T1D patients. DQA1*03 allele was less in the FDRs than in their probands (P < 0.05). GADA was more prevalent in T1D patients carrying DQA1*05-DQB1*0201 or DQA1*03-DQB1*0401 haplotype (55.8% vs 41.0%, 65.5% vs 40.3%, P < 0.05-0.01), whereas IA-2A presented more in the patients carrying DQA1*03-DQB1*0303 haplotype (27.0% vs 7.9%, P < 0.05-0.01), both GADA and IA-2A showed frequently in the patients with DQA1*03-DQB1*0303/DQA1*05-DQB1*0201 haplotypes (34.5% vs 9.7%, P < 0.01). GADA positivity was lower in the patients with DQA1*0102-DQB1*0602 haplotype (16.7% vs 45.9%, P < 0.05). The frequency of IAA was not different between patients with and without susceptible DQ haplotypes (P > 0.05). GADA, IA-2A or IAA presented frequently in FDRs with DQA1*03-DQB1*0303 haplotype. The findings in the study indicate that some of specific HLA-DQA1/-DQB1 genotypes and haplotypes not only confer susceptibility to T1D but also are associated with the presence of the islet autoantibodies in the Han Chinese population.

HLA class I and class II haplotypes in admixed families from several regions of Mexico

We studied HLA class I and class II alleles in 191 Mexican families (381 non-related individuals) to directly obtain the HLA-A/B/DRB1/DQB1 haplotypes and their linkage disequilibrium (LD). The most frequent HLA haplotypes observed were: A*02-B*39-DRB1*04-DQB1*0302, A*02-B*35-DRB1*04-DQB1*0302, A*68-B*39-DRB1*04-DQB1*0302, A*02-B*35-DRB1*08-DQB1*04, A*33-B*1402-DRB1*01-DQB1*05, and A*24-B*35-DRB1*04-DQB1*0302. The four most common haplotypes found by our study involve those previously reported in Amerindian populations. LD analysis of HLA–A-B and HLA-B-DRB1 loci showed significant associations between A29(19)-B44(12), A33(19)-B65(14), A1-B8, A26(19)-B44(12), A24(9)-B61(40), B65(14)-DR1, B8-DR17(3), B44(12)-DR7, B7-DR15(2), and B39(16)-DR4. Also, all DRB1-DQB1 associations showed significant LD values. Admixture estimations using a trihybrid model showed that Mexicans from the State of Sinaloa (Northern Mexico) have a greater proportion of European genetic component compared with Mexicans from the Central area of Mexico, who have a greater percentage of Amerindian genes. Our results are important for future comparative genetic studies of different Mexican ethnic groups with special relevance to disease association and transplantation studies.

Analysis of HLA-DRB1,DQA1,DQB1 haplotypes in Sardinian centenarians

Some genetic determinants of longevity might reside in those polymorphisms for the immune system genes that regulate immune responses. Many longevity association studies focused their attention on HLA (the human MHC) polymorphisms, but discordant results have been obtained. Sardinians are a relatively isolate population and represent a suitable population for association studies. Some HLA-DR and DQ alleles form very stable haplotypes with a strong linkage disequilibrium. In a previous study on Sardinian centenarians we have suggested that HLA-DRB1∗15 allele might be marginally associated to longevity. HLA-DR,DQ haplotypes are in strong linkage disequilibrium and well conserved playing a role in the association to diseases. Hence, we have evaluated, by amplification refractory mutation system/polymerase chain reaction (ARMS-PCR) the HLADQA1 and HLA-DQB1 allele frequencies in 123 centenarians and 92 controls from Sardinia to assess whether the association to HLA-DRB1∗15 allele may be due to the other genes involved in the HLA-DR,DQ haplotypes. The frequencies of HLA-DQA1,DQB1 haplotypes were not significantly modified in centenarians. Nevertheless by evaluating the frequency of DRB1∗15 linked haplotypes, we observed a not significant increase in centenarians of HLA-DQA1∗01,DQB1∗05 and HLA-DQA1∗01,DQB1∗06 haplotypes. These data suggest that these haplotypes might have a role in determining life span expectancy and longevity.

DLA-DRB1, DQA1, and DQB1 Alleles and Haplotypes in North American Gray Wolves

The canine major histocompatibility complex contains highly polymorphic genes, many of which are critical in regulating immune response. Since domestic dogs evolved from Gray Wolves (Canis lupus), common DLA class II alleles should exist. Sequencing was used to characterize 175 Gray Wolves for DLA class II alleles, and data from 1856 dogs, covering 85 different breeds of mostly European origin, were available for comparison. Within wolves, 28 new alleles were identified, all occurring in at least 2 individuals. Three DLA-DRB1, 8 DLA-DQA1, and 6 DLA-DQB1 alleles also identified in dogs were present. Twenty-eight haplotypes were identified, of which 2 three-locus haplotypes, and many DLA-DQA1/DQB1 haplotypes, are also found in dogs. The wolves studied had relatively few dog DLA alleles and may therefore represent a remnant population descended from Asian wolves. The single European wolf included carried a haplotype found in both these North American wolves and in many dog breeds. Furthermore, one wolf DQB1 allele has been found in Shih Tzu, a breed of Asian origin. These data suggest that the wolf ancestors of Asian and European dogs may have had different gene pools, currently reflected in the DLA alleles present in dog breeds.

HLA class II genetic diversity in Arabs and Jews of Iran.

Anthropological studies based on highly polymorphic HLA genes provide useful information for bone marrow donor registry, forensic medicine, disease association studies, as well as designing peptide vaccines against tumors, and infectious or autoimmune diseases. This study was designed to investigate the genetic relationship of Iranian Arabs and Jews using HLA-class II genetic diversity. HLA-DRB1, DQA1, and DQB1 allele frequencies and haplotypes were determined in 134 Iranian Arabs from two different communities and 91 Iranian Jews using PCR/RFLP and PCR/SSP methods. Neighbor-joining analyses showed a closer genetic relationship between Iranian Arabs and Iranian Jews than between either Iranian Arabs and Middle Eastern Arabs or Iranian Jews and other Jews. The results of AMOVA test also revealed no significant difference between these populations and other Iranians. It seems that, Iranian Arabs are originally from the Iranian gene pool and speak Arabic due to their encounter with Arabs. Iranian gene flow to immigrant Jews followed by their expansion in this country may also explain the close genetic relationship among different Iranian ethnic groups.

164-P: Three family members with the same HLA-A, -B, -C, -DRB1 and -DQB1 haplotype containing the recently-discovered B*550103 allele

164-P: Three family members with the same HLA-A, -B, -C, -DRB1 and -DQB1 haplotype containing the recently-discovered B*550103 allele

TNFa‐e Microsatellite, HLA‐DRB1 and ‐DQB1 Alleles and Haplotypes in Brazilian Patients Presenting Recently Diagnosed Type 1 Diabetes Mellitus

TNF microsatellite and HLA class II polymorphisms were studied in 28 recently diagnosed Brazilian patients presenting type 1 diabetes mellitus (T1DM) and in 120 healthy controls. TNFa-e and HLA-DRB1/DQB1 alleles were identified using sets of sequence-specific primers. Compared to controls, the DRB1*03 and DQB1*02 allele groups, TNFa1 allele, and the TNFa4-b5-c1-d4-e3 and TNFa10-b5-c1-d4-e3 haplotypes were overrepresented in patients. TNF microsatellite together with HLA polymorphisms is associated with type 1 diabetes in Brazilian patients, corroborating the participation of the MHC genes in disease susceptibility.

Human leucocyte antigen class II polymorphism in Irish patients with multiple sclerosis

The contribution of human leucocyte antigen (HLA) to the genetic risk for multiple sclerosis (MS) in patients of Northern European Caucasoid ancestry has been known since the 1970s. The northern part of Ireland, including county Donegal, is known to be a high-risk area for the development of MS. Recorded prevalence rates for county Wexford in the south-east Ireland have been markedly lower and suggest the existence of a prevalence gradient within the island. To evaluate the association of HLA-DRB1 and -DQB1 haplotypes with MS in both Wexford and Donegal, we examined a total of 118 patients and 400 regionally matched controls. The aim of this exploratory study was to test the possibility of heterogeneity in HLA class II associations with MS and to identify potential predisposing or protective haplotypes, associated with MS risk in Ireland. We confirmed the association of DRB1*1501-DQB1*0602 haplotype carriage with MS in both Wexford [odds ratio (OR) = 2.95, P= 0.0020, P(cor)= 0.0220] and Donegal (OR = 2.29, P= 0.0030, P(cor)= 0.0420). A higher frequency and a significantly higher homozygosity rate of this haplotype in Donegal are likely contributing factors to the higher prevalence of MS in Donegal compared with Wexford. The distribution of HLA class II alleles among Irish MS patients and controls establishes that there is heterogeneity in HLA class II associations with MS within Ireland.

HLA Alleles and Haplotypes in French North African Immigrants

Human leukocyte antigen (HLA) haplotypes ( n = 187) were genotyped and assigned by the mode of inheritance in migrant families from North Africa who reside in the Paris, France, area. The distribution of alleles and haplotypes in that population was compared with the one obtained in a control population of ancient French natives residing in the same area (248 independent haplotypes also assigned by the mode of inheritance were studied). The results in migrants reveal the following: (1) a higher diversity in the distribution of HLA-A and -DRB1 alleles; (2) lower frequencies of alleles common in our region, such as A*0201 B*1501, B*4001, and DRB1*0401 and increased frequencies of minor subtypes, such as A*3002 and DRB1*0402; and (3) distinct distributions of B/Cw, DRB1/DQB1 or B/Cw/DRB1/DQB1 haplotypes. The results also revealed that the four most frequent five-allele haplotypes in controls i.e., HLA-A*0101/B*0801/Cw*0701/DRB1*0301/DQB1*0201; A*0301/B*0702/Cw*0702/DRB1*1501/DQB1*0602 (both of Indo-Celtic origin); A*2902/B*4403/Cw*1601/DRB1*0701/DQB1*0202 (frequent in Western-Europeans); and A*0201/B*1501/Cw*0304/DRB1*0401/DQB1*0302, represent 10.5% of the total haplotypes in controls but 1.6% in North Africans. Conversely, 9 five-allele haplotypes in multiple copy in North Africans (among which A*3002/B*1801/Cw*0501/DRB1*0301/DQB1*0201 of Paleo-North African origin and A*0201/B*0702/Cw*0702/DRB1*1501/DQB1*0602 of ancient European and Paleo-North African origin) represent 9.6% of the total haplotypes in North Africans but 2.4% in controls. These results thus suggest a low degree of admixture between the two populations.

HLA class II gene polymorphism in Parsees and Zoroastrians of Iran

Extensive polymorphism of the HLA genes in different ethnic groups has been used as an invaluable tool for anthropological studies. In this study, HLA-DRB1, DQA1 and DQB1 allele frequencies and haplotypes were determined in 72 Parsees and 65 Zoroastrians living in Iran. The predominant DRB1 allele was *1103 = 4 in Parsees and *0701 in Zoroastrians. DQA1*0501 was the most common alleles in both spopulations. The most frequent DQB1 allele was *0301 in Parsees and *0201 in Zoroastrians. DRB1*1103 = 4-DQA1*0501-DQB1*0301 and DRB1*0701-DQA1*0201-DQB1*0201 were the most prevalent haplotypes in Parsees and Zoroastrians, respectively. Significant deviation from Hardy-Weinberg equilibrium was observed in DQA1 and DQB1 loci of Zoroastrians. The former locus also departed from neutrality due to balancing selection. All pairs of the studied loci in this study showed significant linkage disequilibrium. Analysis of molecular variance indicated that the main variation was confined to individuals within the studied populations. Neighbour-joining tree based on Nei's genetic distances according to DRB1 and DQB1 allele frequencies showed that Parsees and Zoroastrians of Iran were located in the same cluster of the phylogenetic tree. Furthermore, Zoroastrians of Iran and Pakistan are very close to each other. This study will serve as a reference for further anthropological studies when the HLA profile of all ethnic groups of Iran is investigated.