Allele and haplotype frequencies at human leukocyte antigen class I and II genes in Venezuela's population

Population studies represent an integral part and link in understanding the complex chain of host-pathogen interactions, disease pathogenesis, and MHC gene polymorphisms. Genes of Mongoloid, Caucasoid, and Negroid populations have created a distinctive HLA genetic profile in the Venezuelan population. Our objective was to determine the predominant HLA class I and II alleles and haplotype frequencies in the hybrid population of Venezuela. The study population consisted of 486 healthy unrelated native Venezuelans and 180 families. We examined the frequency of HLA A-B-C, HLA-DQ and HLA-DR genes by polymerase chain reaction and subsequent hybridization with sequence-specific oligonucleotide probes. Phenotypic, allelic and haplotype frequencies were estimated by direct counting and using the maximum-likelihood method. The predominant HLA class I alleles were A*02, A*24, A*68, B*35, B*44, B*51, B*07, B*15 and Cw*07. Regarding HLA class II, the most frequent alleles were DQB1*03 and DRB1*04, DRB1*15, DRB1*13, DRB1*07. The prevailing haplotype was HLA-A*02B*35 DQB1*03 DRB1*04. Some of these alleles and haplotype frequencies were predominantly present in Amerindians (A*02, A*24, B*35, Cw*07, DRB1*04, A*24 B*35). Previous reports have shown high incidence of A*02, B*44, B*51, DRB1*15, DRB1*13, DRB1*07 alleles in several European populations and A*68, B*07, B*15 alleles in African Americans, which could have contributed to the ethnic admixture of the Venezuelan population. We conclude that our results provide strong evidence that Venezuela's population represents an admixture of the primitive Mongoloid Aborigines, Caucasoid Europeans and Western African Negroid migrants.     

Analysis of three RFLPs of the COL1A2 (Type I Collagen) in the Amhara and the Oromo of Ethiopia

Background : The present composition of the Ethiopian population is the result of a complex and extensive intermixing of different peoples of North African, Near and Middle Eastern, and south-Saharan origin. The two main groups inhabiting the country are the Amhara, descended from Arabian conquerors, and the Oromo, the most important group among the Cushitic people. With the exception of some surveys on the general Ethiopian populations, little is known about the degree of genetic differentiation between the Amhara and the Oromo. Aim : The study seeks to investigate the genetic structure of these two heterogeneous Ethiopian populations and to characterize their relationships with other African and Mediterranean peoples. Subjects and methods : Amhara and Oromo individuals ( n = 171) were analysed for three RFLPs (restriction fragment length polymorphisms) of the COL1A2 gene. To better define the genetic relationship between the two Ethiopian groups, and also between African and non-African peoples, genetic distances among Amhara, Oromo and other populations were estimated using the COL1A2 allele and haplotype frequencies, and the allele frequencies of 16 additional classical markers. Results : &#104 2 analysis applied to the COL1A2 allele and haplotype frequencies showed a small but statistically significant degree of heterogeneity between the two Ethiopian populations. Combining the information obtained from the three RFLP markers, a significant level of differentiation (Fst = 0.0147, p = 0.036) was also detected between Amhara and Oromo. The genetic distance analysis showed the separation between African and non-African populations, with the Amhara and Oromo located in an intermediate position. This pattern is consistent with the location of the two Ethiopian groups in other genetic analysis and with cultural data. Conclusions : The present findings suggest the presence of a differential level of genetic relatedness with south-Saharan peoples in the two Ethiopian groups, which could reflect their different history and seems to indicate the existence of genetic sub-structure within the country.     

Ethiopia: between Sub-Saharan Africa and Western Eurasia

Ethiopia is central to population genetic studies investigating the out of Africa expansion of modern humans, as shown by Y chromosome and mtDNA studies. To address the level of genetic differentiation within Ethiopia, and its relationship to Sub‐Saharan Africa and Eurasia, we studied an 8kb segment of the X‐chromosome from 72 chromosomes from the Amhara, Oromo and Ethiopian Jews, and compared these results with 804 chromosomes from Middle Eastern, African, Asian and European populations, and 22 newly typed Saharawi. Within Ethiopia the two largest ethnic groups, the Amhara and Oromo, were not found to be statistically distinct, based on an exact test of haplotype frequencies. The Ethiopian Jews appear as an admixed population, possibly of Jewish origin, though the data remain equivocal. There is evidence of a close relationship between Ethiopian and Yemenite Jews, likely a result of indirect gene flow. Within an African and Eurasian context, the distribution of alleles of a variable T_n repeat, and the spread of haplotypes containing Africa‐specific alleles, provide evidence of a genetic continuity from Sub‐Saharan Africa to the Near East, and furthermore suggest that a bottleneck occurred in Ethiopia associated with an out of Africa expansion. Ethiopian genetic heterogeneity, as evidenced by principal component analysis of haplotype frequencies, most likely resulted from periods of subsequent admixture. While these results are from the analysis of one locus, we feel that in association with data from other marker systems they add a complementary perspective on the history of Ethiopia.     

Analysis of three RFLPs of the COL1A2 (Type I Collagen) in the Amhara and the Oromo of Ethiopia

BACKGROUND: The present composition of the Ethiopian population is the result of a complex and extensive intermixing of different peoples of North African, Near and Middle Eastern, and south-Saharan origin. The two main groups inhabiting the country are the Amhara, descended from Arabian conquerors, and the Oromo, the most important group among the Cushitic people. With the exception of some surveys on the general Ethiopian populations, little is known about the degree of genetic differentiation between the Amhara and the Oromo. AIM: The study seeks to investigate the genetic structure of these two heterogeneous Ethiopian populations and to characterize their relationships with other African and Mediterranean peoples. Subjects and methods: Amhara and Oromo individuals (n = 171) were analysed for three RFLPs (restriction fragment length polymorphisms) of the COL1A2 gene. To better define the genetic relationship between the two Ethiopian groups, and also between African and non-African peoples, genetic distances among Amhara, Oromo and other populations were estimated using the COL1A2 allele and haplotype frequencies, and the allele frequencies of 16 additional classical markers. RESULTS: chi(2) analysis applied to the COL1A2 allele and haplotype frequencies showed a small but statistically significant degree of heterogeneity between the two Ethiopian populations. Combining the information obtained from the three RFLP markers, a significant level of differentiation (Fst = 0.0147, p = 0.036) was also detected between Amhara and Oromo. The genetic distance analysis showed the separation between African and non-African populations, with the Amhara and Oromo located in an intermediate position. This pattern is consistent with the location of the two Ethiopian groups in other genetic analysis and with cultural data. CONCLUSIONS: The present findings suggest the presence of a differential level of genetic relatedness with south-Saharan peoples in the two Ethiopian groups, which could reflect their different history and seems to indicate the existence of genetic sub-structure within the country.     

Major histocompatibility complex class II (HLA-DRB and -DQB) allele frequencies in Botswana: association with human immunodeficiency virus type 1 infection

Southern Africa is facing an unprecedented public health crisis due to the high prevalence of human immunodeficiency virus type 1 (HIV-1). Vaccine development and testing efforts, mainly based on elicitation of HIV-specific T cells, are under way. To understand the role of human leukocyte antigen (HLA) class II alleles in HIV pathogenesis and to facilitate HLA-based HIV-1 vaccine design, we analyzed the frequencies of HLA class II alleles within the southern African country of Botswana. Common HLA class II alleles were identified within the Botswana population through the molecular genotyping of DRB and DQB1 loci. The DRB1 allele groups DRB1*01, DRB1*02/15, DRB1*03, DRB1*11, and DRB1*13 were encountered at frequencies above 20%. Within the DQB1 locus, DQB1*06 (47.7%) was the most common allele group, followed by DQB1*03 (39.2%) and DQB1*04 (25.8%). We found that DRB1*01 was more common in HIV-negative than in HIV-positive individuals and that those who expressed DRB1*08 had lower median viral loads. We demonstrate that the frequencies of certain HLA class II alleles in this Botswana population differ substantially from those in North American populations, including African-Americans. Common allele groups within Botswana cover large percentages of other African populations and could be targeted in regional vaccine designs.     

HLA class I and class II of the Nivkhi, an indigenous population carrying HTLV-I in Sakhalin, Far Eastern Russia

Abstract: The Nivkhi are a native people isolated in the Nogliki region of Sakhalin, Far East Russia, where our group recently recognized human T-cell lymphoma virus type I (HTLV-I) infection. In order to trace the Nivkhi's ethnic background and the HTLV-I carriers, we investigated HLA class I and II allele types of 53 Nivkhi (including four HTLV-I carriers). Major HLA class I alleles of the Nivkhi were A*24, A*02, B*40, B*48, B*27, B*35 with allele frequencies similar to the Orochon, a native people isolated in Northeast China. Major Nivkhi class II alleles were DRBl*0901, DRB1*1401, DRB1*1201, DRB1*1106 with allele frequencies similar to the Ainu in Hokkaido, Japan, but dissimilar to other Asian Mongoloids, including the general Japanese population. The same HLA class I and II allele frequencies are found in both Nivkhi HTLV-I carriers and the background population. A dendrogram of HLA class I alleles showed that the Nivkhi were closely related to the Orochon and Yakut, and remotely related to the Japanese, Ainu and other Asian Mongoloids. Interestingly, the Nivkhi were intermediately related to the Amerindians (Inuit, Tlingit and Andeans), a relationship closer than to the Japanese and Asian Mongoloids. These results suggested the Nivkhi might be related to some genetic group of Northeast Asian Mongoloids like the Orochon and Yakut, being infected with HTLV-I in the distant past before diverging into the current major Mongoloid ethnic groups.     

Survey of seven plasma protein polymorphisms in the Amhara and Oromo populations of Ethiopia

The Ethiopian population is very difficult to specify due to a very high degree of intermixing among different peoples. The two groups of the present study, the Amhara and Oromo, constitute 38% and 35% of the population, respectively. In order to investigate the genetic composition of the Amhara and Oromo, genetic polymorphisms of seven plasma proteins (F13A, F13B, ORM1, AHSG, C6, C7, and APOC2), already identified as useful anthropological markers, were studied. No statistically relevant differences were found between the two groups for all of the systems examined. ORM1 and F13A showed frequencies in the range observed in other populations of Caucasoid and Negroid origin. F13B, AHSG, and C6 displayed gene frequencies and a number of variant alleles that seem particular to these two groups. No variation was observed for C7 and APOC2. Correspondence and distance analyses were used to interpret and compare the gene frequencies of the Amhara and Oromo with those of other related populations. These methods locate Ethiopians in an intermediate position between African Blacks and a group of Caucasoid populations, confirming cultural and historical data. © 1994 Wiley-Liss, Inc.     

Relative HLA-DRB1*13 allele frequencies and DRB3 associations of unrelated individuals from five US populations

The frequencies of 30 HLA-DRB1*13 alleles and 15 DRB3 alleles were determined for the 5 major U.S. ethnic populations: Caucasians, African Americans, Asian/Pacific Islanders, Hispanics, and Native Americans. A random sampling (163) of DRB1*13-positive individuals from each self-described ethnic group was selected out of a pool of 82,979 unrelated individuals, providing at least an 80% probability of detecting a rare allele that occurred at 1%. These 815 samples were subjected to allele-level SSOP typing and/or DNA sequencing which identified 11 different DRB1*13 alleles. DRB1*1301 and DRB1*1302 were the most common alleles seen in the five major ethnic groups while DRB1*1304 was not detected among Caucasians and DRB1*1305 was not detected among African Americans. DRB1*13 allele diversity was surprisingly more limited among African Americans compared to both Caucasians and Asian/Pacific Islanders. To determine the extent of DRB1*13-DRB3 associations, 504 of these samples expressing only one DRB3-associated DRB1 allele were subjected to PCR-SSOP typing and 14 DRB1*13-DRB3 haplotypes were detected. The distribution revealed that African Americans were significantly different from Caucasians, Asian/Pacific Islanders, and Hispanics. Allele frequency studies such as this further support previous findings that the distribution of HLA types can differ significantly among different ethnic populations.     

The Frequency of HLA Class I and II Alleles in Pakistani Patients with Aplastic Anemia

Hematological disorders like Aplastic anemia are quite frequent in Pakistan. Human leukocyte antigen (HLA) system, have been implicated in the development of Aplastic anemia in various population-based studies, The aim of this study was to determine the role of the HLA Class I and Class II alleles in genetic susceptibility to Aplastic anemia in Pakistani patients. HLA A*, B* and DRB1* alleles were analyzed, in 61 Pakistani patients (Females n = 22, Males n = 39) and the control group consisted of 200 ethnically matched individuals (Females n = 89, Males n = 111). The allele frequency of DRB1*15 was found significantly higher in patients 0.36 (p = 0.001 with odds ratio = 1.97), as compared to the controls 0.212. Although DRB1*03 percent frequency was significantly higher in controls 0.175 (p = 0.023) with odds ratio = 0.514, as compared to patients 0.106.Therefore DRB1*15 emerged as a susceptible allele and DRB1*03 as a protective allele in Pakistani Aplastic anemia patients and control samples. No significant difference was found in allele frequencies of other HLA class I and HLA class II alleles for both patients and controls. Three haplotypes A*02 B*40 DRB1*15 (p = 0.021), A*31 B*51 DRB1*13 (p = 0.12) and A*33 B*58 DRB1*15 (p = 0.000) showed significant variations in the two groups.     

African-American HLA class II allele and haplotype diversity

Molecular genetic techniques were used to type nine loci in the HLA class II region in 241 unrelated African-Americans from New York City (NYC). Several effects attributable to recent genetic admixture were evident: the number of distinct class II alleles and haplotypes was larger in the African-Americans than in people of African or European origin, the allele frequencies were more consistently even, and linkage disequilibrium was present across the entire class II region. The African-American DRB1 allele frequencies almost always fell between frequencies among samples from northern Europe and the Gambia, two possible founding populations. The exceptions are attributed to the contribution of other genetically dissimilar African groups to the African-American gene pool. DRB1 allele frequencies (specifically DRB 1*1501) and some haplotypes of DRB 1-DPB1 were different in our NYC and the 11th International Histocompatibility Workshop (IHW) samples of African-Americans. The high level of allele and haplotype diversity found in African-Americans has important implications for the construction of pools of unrelated potential donors for tissue transplantation.     

HLA class II disease associations in southern Africa

Southern Africa harbors several population groups representing a diversity of gene pool origins. This provides a unique opportunity to study genetic disease predisposition in these populations against a common environmental background. Human leukocyte antigen (HLA) association studies of these populations could improve knowledge on inter-population variation and HLA-related disease susceptibility. The aim of this paper is to review HLA class II disease associations reported for southern African population groups, compare them with findings in other populations and identify those unique to southern Africa. A number of HLA class II disease associations appear to be unique to southern African populations. These include DRB1*14011 association with insulin-dependent diabetes mellitus susceptibility in the Xhosa and DRB1*10 and DQB1*0302 with rheumatoid arthritis susceptibility in the South African (SA) Indian and SA Coloreds, respectively. A noteworthy similarity in class II disease association was observed among southern African Caucasoid and their European parental populations. Unique HLA class II disease associations observed in southern Africa are consistent with the notion that unique environmental and natural selective factors have resulted in certain ethnic-specific HLA class II disease associations, while common HLA class II disease associations found across different populations support the notion that common diseases are caused by common, ancient alleles present in indigenous African populations.     

African-American HLA class II allele and haplotype diversity

Molecular genetic techniques were used to type nine loci in the HLA class II region in 241 unrelated African-Americans from New York City (NYC). Several effects attributable to recent genetic admixture were evident: the number of distinct class II alleles and haplotypes was larger in the African-Americans than in people of African or European origin, the allele frequencies were more consistently even, and linkage disequilibrium was present across the entire class II region. The African-American DRB1 allele frequencies almost always fell between frequencies among samples from northern Europe and the Gambia, two possible founding populations. The exceptions are attributed to the contribution of other genetically dissimilar African groups to the African-American gene pool. DRB1 allele frequencies (specifically DRB1*1501) and some haplotypes of DRB1-DPB1 were different in our NYC and the 11th International Histocompatibility Workshop (IHW) samples of African-Americans. The high level of allele and haplotype diversity found in African-Americans has important implications for the construction of pools of unrelated potential donors for tissue transplantation.     

Frequencies of allele groups HLA‐A,HLA‐B and HLA‐DRB1 in a population from the northwestern region of São Paulo State,Brazil

The aim of this study was to estimate the HLA‐A, HLA‐B and HLA‐DRB1 allele groups frequencies in a population of 1559 volunteer bone marrow donors from the northwestern region of São Paulo State grouped according to ethnicity. An additional objective was to compare the allele frequencies of the current study with data published for other Brazilian populations. The allele groups were characterized by the PCR‐rSSO method using Luminex^® technology. Twenty HLA‐A, 32 HLA‐B and 13 HLA‐DRB1 allele groups were identified. The most common allele groups in European descent and mixed African and European descent samples were HLA‐A*02, HLA‐B*35 and HLA‐DRB1*13, while HLA‐A*02, HLA‐B*35 and HLA‐DRB1*11 were more common in African descent samples. The HLA‐A*23, HLA‐A*36, HLA‐B*58 and HLA‐B*81 allele groups were more common in sample from African descent than European descent, and the HLA‐DRB1*08 was more common in mixed African and European descent than in European descent. Allele group frequencies were compared with samples from other Brazilian regions. The HLA‐A*30 and HLA‐A*23 were more common in this study than in the populations of Rio Grande do Sul and Paraná; and the HLA‐A*01, HLA‐B*18, HLA‐B*57 and HLA‐DRB1*11 were more common in this study than in the population of Piauí. The least frequent allele groups were HLA‐A*31, HLA‐B*15, HLA‐B*40 and HLA‐DRB1*08 for the population of Piauí, HLA‐A*01 and HLA‐A*11 for Parana, HLA‐A*02 and ‐A*03 for Rio Grande do Sul and HLA‐DRB1*04 for Paraná, Rio Grande do Sul and Piauí. These data provide an overview on the knowledge on HLA diversity in the population of the northwestern region of São Paulo State and show that the genes of this system are useful to distinguish different ethnic groups.     

HLA class I and class II DNA typing and the origin of Basques

Abstract: Seven HLA class I and class II loci (HLA-A, B, C, DRB1, DQA1, DPA1 and DPB1) were typed at the DNA level in two populations of the Iberian Peninsula (100 Basque and 88 Catalan individuals) in order to unravel their genetic relationship and to compare these results with other European and Mediterranean populations. For the first time,- the frequencies of alleles and haplotypes for the class I HLA loci at the DNA level in these populations are presented. The most frequent haplotype in both populations is A*29-Cw*1601-B*44-DRB1*0701-DQA1*0201-DPA1*0103-DPB1*0401. Neither population differed markedly from the highly homogeneous European and Mediterranean genetic landscape. The Basques, a European outlier population according to classical genetic markers, appear to lie within the genetic European variation with a slight uniqueness and show no clear relationship to North African populations, as has been postulated in some previous HLA studies. Here, the range of possibilities provided by the highly polymorphic HLA system is stressed by using genetic distances, phylogenetic trees and principal component analyses in order to reconstruct population history.     

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     

Pemphigus and HLA in Morocco.

PURPOSE OF STUDY: Pemphigus is a group of autoimmune bullous dermatosis diseases characterized by autoantibodies against keratinocyte adhesion molecule. A significant association with HLA class II genes, particularly DR4 and DR14 has been described in many ethnic groups and countries. We have investigated, for the first time in Morocco the relationship between different pemphigus subtypes and HLA genes. PATIENTS AND METHODS: Fifty-two unrelated patients were compared to 178 healthy controls matched by age, sex and ethnic origin. HLA typing was performed by standard complement dependent microlymphocytotoxic method for class I and by sequence-specific primer amplification method for class II. RESULTS: No significant association was observed with any of the HLA-A or -B antigens. Generic typing showed a significant increase of DRB1*04 (p=0.002), DRB1*14 (p=0.003) and DQB1*03 (p=0.02) allele frequencies and significant decrease of DRB1*15 (p<0.0001) and DQB1*06 (p=0.01) allele frequencies. HLA-DRB1*15-DQB1*06 haplotype seems to confer a protective effect in our population while DRB1*04-DQB1*03 and DRB1*14-DQB1*05 haplotypes induced susceptibility to the disease. CONCLUSION: Taken together, our results confirmed the genetic predisposition to pemphigus. However, genetic factors are not sufficient to explain the high prevalence of pemphigus observed in the Moroccan population since alleles of susceptibility were similar to those commonly described in other populations throughout the world.     

HLA class II polymorphism in a Gabonese Banzabi population

The HLA class II typing of 167 unrelated Gabonese individuals from the Banzabi ethnic group was assessed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The most frequent alleles at each locus were DRB1*1501-3 (0.31), DQA1*0102 (0.50), DQB1*0602 (0.42) and DPB1*0402 (0.29). The estimation of the haplotype frequencies as well as the observation of the segregation of several haplotypes using additional HLA typing of relatives, revealed that the three-locus haplotype DRB1*1501-3-DQA1*0102-DQB1*0602 was found at the highest frequency (0.31) among these individuals. This haplotype is not typically African and has already been described in Caucasians, but its presence at high frequency is exclusive to populations originating from Central Africa, and can thus be designated as a particular genetic marker of these populations.     

HLA class II similarities in Iranian Kurds and Azeris

The genetic relationship between Kurds and Azeris of Iran was investigated based on human leukocyte antigen (HLA) class II profiles. HLA typing was performed using polymerase chain reaction/restriction fragment-length polymorphism (PCR/RFLP) and PCR/sequence-specific primer (PCR/SSP) methods in 100 Kurds and 100 Azeris. DRB1*1103/04, DQA1*0501 and DQB1*0301 were the most common alleles and DRB1*1103/04-DQA1*0501-DQB1*0301 was the most frequent haplotype in both populations. No significant difference was observed in HLA class II allele distribution between these populations except for DQB1*0503 which showed a higher frequency in Kurds. Neighbor-joining tree based on Nei's genetic distances and correspondence analysis according to DRB1, DQA1 and DQB1 allele frequencies showed a strong genetic tie between Kurds and Azeris of Iran. The results of amova revealed no significant difference between these populations and other major ethnic groups of Iran. No close genetic relationship was observed between Azeris of Iran and the people of Turkey or Central Asians. According to the current results, present-day Kurds and Azeris of Iran seem to belong to a common genetic pool.     

Relationship of type 1 diabetes to ancestral proportions and HLA DR/DQ alleles in a sample of the admixed Cuban population

Background: Incidence of type 1 diabetes varies widely around the world, probably due to ethnic differences across populations among other factors.

Aims: To determine whether there is an association between disease and ancestry proportions; and to control disease–HLA associations for possible confounding by admixture or population stratification.

Subjects and methods: 100 cases and 129 controls participated in the study. Ancestry informative markers, which have considerable differences in frequency between European, West African and Native American populations were used. Type 1 diabetes associated HLA susceptibility/protection alleles were ascertained by PCR using specific primers. Statistical analyses were conducted using STRUCTURE 2.1, ADMIXMAP 3.7, SPSS 16.0 and STRAT 1.0 packages.

Results: The results of logistic regression implemented in ADMIXMAP 3.7 indicated that European ancestry was associated with type 1 diabetes mellitus with an odds ratio of 5.7 corresponding to one unit change in European admixture proportion. Association was found between HLA alleles and disease, DQA1*0501, *0301 DQB1*0201 and DRB1*0301, *0401 being susceptibility alleles and DRB1*1501, DQA1*0102/3 and DQB1*0602 being protective alleles.

Conclusions: We found an association between European ancestry and type 1 diabetes in our sample, indicating the contribution of ethnicity to incidence differences. Previously reported associations of HLA DR/DQ alleles with disease are confirmed for the admixed Cuban population.     

Susceptible and protective associations of HLA DRB1*/DQB1* alleles and haplotypes with ischaemic stroke

Stroke has emerged as the second commonest cause of mortality worldwide and is a major public health problem. For the first time, we present here the association of human leucocyte antigen (HLA)‐DRB1*/DQB1* alleles and haplotypes with ischaemic stroke in South Indian patients. Ischaemic stroke (IS) cases and controls were genotyped for HLA‐DRB1*/DQB1* alleles by polymerase chain reaction sequence‐specific primers (PCR‐SSP) method. The frequencies of HLA class II alleles such as DRB1*04, DRB1*07, DRB1*11, DRB1*12, DRB1*13, DQB1*02 and DQB1*07 were high in IS patients than in the age‐ and gender‐matched controls, suggesting that the individuals with these alleles are susceptible to ischaemic stroke in South India. The frequencies of alleles such as DRB1*03, DRB1*10, DRB1*14, DQB1*04 and DQB1*05 were less in IS cases than in the controls, suggesting a protective association. Haplotypes DRB1*04‐DQB1*0301, DRB1*07‐DQB1*02, DRB1*07‐DQB1*0301, DRB1*11‐DQB1*0301 and DRB1*13‐DQB1*06 were found to be high in IS patients conferring susceptibility. The frequency of haplotype DRB1*10‐DQB1*05 was high in controls conferring protection. IS‐LVD and gender‐stratified analysis too confirmed these susceptible and protective associations. Thus, HLA‐DRB1*/DQB1* alleles and haplotypes strongly predispose South Indian population to ischaemic stroke. Further studies in different populations with large sample size or the meta‐analysis are needed to explain the exact mechanism of associations of HLA gene(s) with IS.