HLA class II allele frequencies in the Lebanese population

Human leukocyte antigens (HLA) allele determination is becoming an increasingly important aspect in the field of transplantation as well as in the area of HLA association with a number of diseases. Through Lebanon's history, this country, situated at a crossroads between Europe, Asia and Africa, has been a host for various populations of different ethnicities. The aim of our study is to determine whether allele polymorphisms in the Lebanese population present a distinguishing feature. Although data on HLA phenotypic polymorphisms in Lebanon have been reported in the literature, our study is the first to examine frequencies of HLA polymorphisms in the country at the molecular level. Allele frequencies of the Lebanese population were analyzed and compared with those of other populations. HLA class II genotyping of DRB1* and DQB1* loci by PCR-sequence-specific primer (SSP) was performed on 191 unrelated Lebanese subjects of both sexes and of different regions and sects in Lebanon. The study revealed that DRB1*1101, DRB1*0401 and DRB1*0301 were the three most common DRB1* alleles observed (respective allele frequencies of 0.302, 0.164 and 0.096). In the DQB locus allele group, DQB1*0301 (allele frequency of 0.384) was highly predominant followed by the DQB1* 0501, DQB1*0201 and DQB1*0302 with respective allele frequencies of 0.199, 0.195 and 0.103. These results confirm previous serological studies and show the high prevalence of DRB1*1101 and DQB1*0301 in Lebanon, which could be explained by the high frequency of consanguineous marriages in the population. The presence of other common alleles is consistent with historical data showing that the Lebanese population is an admixture of various ethnicities.     

HLA class I polymorphisms in Tunisian patients with otosclerosis

Background: Otosclerosis is a common form of hearing impairment among Western-Eurasian adults. The cause of otosclerosis remains unknown. Autoimmune reaction against the otic capsule has been suggested as a possible aetiologic factor in otosclerosis.

Aim: The present study is the first report to evaluate the relationship between class I major histocompatibility complex (MHC) genes (HLA-A, HLA-B and HLA-Cw) and genetic susceptibility to otosclerosis in Tunisian patients.

Subjects and methods: Fifty unrelated Tunisian patients exhibiting clinical otosclerosis were typed for HLA-A, HLA-B and HLA-Cw antigens and compared with 100 ethnically-matched healthy controls.

Results: Increased frequencies of HLA-A*03 (OR = 4.16, Pc < 0.043), HLA-B*35 (OR = 2.76, Pc < 0.043) and HLA-Cw*03 (OR = 4.57, Pc < 0.043) antigens were found in the patients with otosclerosis compared with healthy controls. Individuals with HLA-A*30 (OR = 0.25, Pc < 0.043), HLA-B*51 (OR = 0.11, Pc < 0.043), HLA-Cw*16 (OR = 0.08, Pc < 0.043) and Cw*06 (OR = 0.32, Pc < 0.043) antigens have a protective effect against otosclerosis.

Conclusions: In conclusion, the data suggest that a variation in class I HLA antigens could be a genetic factor involved in susceptibility to otosclerosis in the Tunisian population.     

HLA class I and class II polymorphisms in Tunisian Berbers

Background: The HLA polymorphism is a powerful genetic tool to study population origins. By analysing allele frequencies and haplotypes in different populations, it is possible to identify ethnic groups and establish the genetic relationships among them.

Aim: The Berber (endogenous Tunisians) HLA class I and class II genotypes were analysed and compared with those of Mediterranean and Sub-Saharan African communities using genetic distances, Neighbour-Joining dendrograms, correspondence and haplotype analysis.

Subjects and methods: One hundred and five unrelated Berbers were typed for HLA class I (A, B) and class II (DRB1, DQB1) gene alleles using reverse dot-blot hybridization.

Results: High frequencies of A*0201 (24.76%), A*3402 (22.38%) and B*44 (32.85%) alleles were recorded for Berbers, the highest recorded for Mediterranean and North African populations. This study shows a close relatedness of Tunisian Berbers to other Tunisians, North Africans and Iberians.

Conclusion: The apparent relatedness of Tunisian Berbers to present-day (North African) Tunisians, Algerians and Moroccans suggests that the Arab invasion of North Africa (7^th–11^th centuries AD) did not significantly impact the genetic makeup of North Africans. Furthermore, Tunisian Berbers appear to be closely related to Iberians (Spaniards and Basques), indicating that the 7^th century AD gene flow of invaders was low in Iberians and that the main part of their genetic pool came after the Northward Saharan migration, when hyper-arid conditions were established in Sahara (before 6000 BC). Other studied populations belong to the old Mediterranean substratum, which has been present in the area since pre-Neolithic times. This study indicates a higher proportion of Iberian than Arab ancestry in Tunisian Berbers, which is of value in evaluating the evolutionary history of present-day Tunisians. Greeks seem to share genetic HLA features (Chr 6) with Sub-Saharans. The relatedness of Greeks to Sub-Saharans has been confirmed by other studies based on chromosome 7 genetic markers.     

HLA analysis of the Parsi (Zoroastrian) population in Pakistan

The Parsis of Pakistan are descendants of Zoroastrians from Iran who fled to Gujarat in India after the Arab invasion in 900 AD. A small group eventually migrated from India to Karachi in Pakistan. In this study, the Parsis from Pakistan were analyzed at the HLA-B, -C, -DRB1 and -DQB1 loci using the polymerase chain reaction with sequence-specific primers (PCR-SSP). The most common alleles at the HLA loci were HLA-B*35 (15.9%), HLA-Cw*0602 (21.4%), HLA-DRB1*11 (23.0%), and HLA-DQB1*02 (24.7%). Data analysis suggests that the Parsis of Pakistan and India descended from the same stock and may have the closest ancestry with Jewish and Italian populations.     

Characteristics of HLA class I and class II polymorphisms in Rwandan women

OBJECTIVE: To define HLA class I and class II polymorphisms in Rwandans. METHODS: PCR-based HLA genotyping techniques were used to resolve variants of HLA-A, B, and C to their 2- or 4-digit allelic specificities, and those of DRB1 and DQB1 to their 4- or 5-digit alleles. RESULTS: Frequencies of 14 A, 8 C, and 14 B specificities and of 13 DRB1 and 8 DQB1 alleles were >/=0.02 in a group of 280 Rwandan women. These major HLA factors produced 6 haplotypes extending across the class I and class II regions: A*01-Cw*04-B* 4501-DRB1*1503-DQB1*0602 (A1-Cw4-B12- DR15 - DQ6), A * 01 - Cw * 04 - B * 4901 -DRB1 * 1302-DQB1*0604 (A1-Cw4-B21-DR13-DQ6), A*30 - Cw*04 - B*15 - DRB1*1101 - DQB1*0301 (A19-Cw4-B15-DR11-DQ7), A*68-Cw*07-B* 4901-DRB1*1302-DQB1*0604(A28-Cw7-B21- DR13 - DQ6), A*30 - Cw*07 - B*5703 - DRB1* 1303-DQB1*0301(A19 - Cw7 - B17 - DR13 - DQ7), and A*74-Cw*07-B*4901-DRB1*1302-DQB1* 0604 (A19-Cw7-B21-DR13-DQ6), respectively. Collectively, these extended haplotypes accounted for about 19% of the total. Other apparent class I-class II haplotypes (e.g., Cw*17-B*42-DRB1*0302-DQB1*0402, Cw*06- B*58-DRB1*1102-DQB1*0301, and Cw*03- B*15-DRB1*03011-DQB1*0201) did not extend to the telomeric HLA-A locus, and other 3-locus class I haplotypes (e.g., A*68-Cw*04-B*15, A*74-Cw*04-B*15, and A*23-Cw*07-B*4901) completely or partially failed to link with any specific class II alleles. DISCUSSION: Frequent recombinations appeared to occur between the three evolutionarily conserved HLA blocks carrying the class I and class II loci. The HLA class I profile seen in Rwandans was not directly comparable with those known in the literature, although the class II profile appeared to resemble those in several African populations. These data provide additional evidence for the extensive genetic diversity in Africans.     

HLA class I and class II allele distribution in the Peruvian population

The distribution of HLA-A, -B, -C, -DRB1 and -DQB1 alleles in the Peruvian population was studied and compared with those of other populations in order to provide further information about their anthropological origin. Our data are consistent with the Mestizo character of this population. In terms of genetic distance Peruvians are closest to Bolivians, which is in agreement with the geographical location and the cultural and anthropological background of the two human groups. Several HLA-B alleles originally described in genetically isolated Amerindian tribes are also present in the sample studied here. This fact and the reported finding of these alleles in several Amerindian groups suggests that they were present in the first wave of humans that populated South America (Paleoindians) before they split to give rise to the different South American tribes.     

HLA class I and class II polymorphisms in Saudi patients with myasthenia gravis

Myasthenia gravis (MG) is a rare autoimmune disease of the neuromuscular junction. MG has been shown to be associated with many HLA antigens in different populations. Here we have analysed the frequency of HLA‐A, B, DR and DQ in a group of Saudi MG patients and compared their results to a group of healthy controls. MG in Saudi patients is found to be associated with HLA‐A*23, B*08, B*18, DRB1*16 and DRB1*13. The strongest association was with HLA‐B*08, which was associated with young age at onset and female gender. Our results are in line with other published results from around the world and warrant fine mapping of the area using microsatellite to map the disease gene.     

Associated expression of HLA class I and class II antigens on melanoma cells in surgically removed metastases

Malignant transformation of melanocytes and further neoplastic progression may be associated with qualitative and/or quantitative changes in expression of HLA class I and class II antigens. Since previous immunohistochemical studies of surgically removed melanoma lesions have suggested a relationship in the expression of HLA class I and class II antigens, we have investigated the expression of these antigens at the single cell level. Double immunofluorescence staining of frozen sections of melanoma metastases and immunoelectron microscopic double labelling of melanoma cell suspensions prepared from three of these lesions has detected three HLA phenotypes on the large majority of melanoma cells: either both HLA class I and class II antigens, neither HLA antigen or only HLA class I antigens. In four out of the 11 lesions a few melanoma cells were found to express HLA class II antigens and to lack HLA class I antigens. A relationship was also found in the level of expression of HLA class I and class II antigens, as estimated by the intensity of staining with monoclonal antibodies. The level of expression of HLA class II antigens appeared to be similar to or lower than that of HLA class I antigens on the large majority of melanoma cells. This coordinated heterogeneity in the expression of HLA class I and class II antigens by melanoma cells may have implications in the interactions of tumour cells with the host's immune system.     

HLA polymorphism in six ethnic groups from Pakistan

The extreme polymorphism found at some of the loci of the HLA system has made it an invaluable tool for population genetic analyses. In this study the genetic polymorphism of six Pakistani ethnic groups was investigated at the HLA-A, -B, -C, -DRB and DQB1 loci using polymerase chain reaction with sequence specific primers. The groups included in this study are the Baloch, Brahui and Sindhi from the south and the Burusho, Kalash and Pathan from the north of Pakistan. The allele frequencies, three-locus haplotype frequencies for HLA-A, -C, -B and HLA-A, -B, -DRB1 are given. Variation in the allele and haplotype distribution between the six Pakistani ethnic groups was observed. A phylogenetic tree and correspondence analysis based on HLA-A, -B, -C, -DRB1 and -DQB1 allele frequencies revealed the Kalash population to be distinct from the remaining Pakistani populations. The Baloch and Brahui were closely related to one another. The Sindhi were closer to the Pathan and Burusho populations than to the neighboring Baloch and Brahui populations, indicating admixture between the northern and southern populations of Pakistan. A phylogenetic tree and correspondence analysis comparing the Pakistani populations with various other world populations showed that the Pakistani ethnic groups lie within the cluster of Asian Indian populations. The three-locus haplotypes found in the Pakistani populations suggest an influence from Caucasian and Oriental populations.     

HLA class II involvement in HIV-associated Toxoplasmic encephalitis development

A total of 220 individuals were included in this study, 112 HIV-seronegative healthy individuals and 108 HIV-1-infected patients involving: 18 AIDS patients with Toxoplasmic encephalitis (AIDS-TE), 49 AIDS patients without TE, and 41 asymptomatic patients, were genotyping for DR and DQ loci by molecular biology techniques. Fisher's Exact test was used for statistical analysis. HLA-DQB*0402 and DRB1*08 alleles were associated with a high risk to develop opportunistic infections with neurological involvement, mainly Toxoplasma encephalitis in relationship with subjects healthy (OR = 20.43; Pc = 7.0 x 10(-6) and OR = 11; Pc = 2.6 x 10(-4), respectively); in relationship with AIDS no TE (OR = 6.98; Pc = 0.028 and OR = 4.85; P = 0.012, Pc = 0.14) and with patients in asymptomatic stage (OR = 61.50, Pc = 8.4 x 10(-6) and OR = 19.38; Pc = 3.9 x 10(-4)), respectively. CONCLUSIONS: It was concluded that the presence of HLA-DQB*0402 and DRB1*08 alleles in HIV-1-positive patients could be considered risk factors for developing neurological opportunistic infections, mainly Toxoplasmic encephalitis.     

HLA class I and class II polymorphism in a population from south-eastern Tunisia (Gabes Area)

The gene frequencies of HLA class I and class II alleles were investigated in 95 healthy Tunisian individuals from Gabes. Our aim was to compare the genetic relationship between Gabesians and Mediterraneans and sub-Sahara Africans using genetic distances, Neighbour-Joining dendrograms, correspondence and haplotypes analysis, thereby providing additional information about evolutionary history of modern-day Tunisians. Subjects were unrelated and of both genders, and HLA class I and class II genes were genotyped using the polymerase chain reaction-sequence specific primer (PCR-SSO) technique. Our data show that south-eastern Tunisians (Gabes area) are related to present-day North Africans (Algerians, Moroccans, Tunisians) and Iberians (Spaniards, Basques), and along with other North Africans, appear to be genetically related to Berbers, an indication that the Arab invasion (7th-11th centuries) of North Africa had minimal contribution on the HLA makeup of North Africans. On the other hand, Iberians including Spaniards and Basques show relatedness to (native Tunisian) Berbers, suggesting that the gene flow of 7th century AD invaders was also low in Iberians. In conclusion, the successive invasions of North Africa in general, and Tunisia in particular, did not modify markedly the genetic makeup of present-day Tunisians. With the exception of Greeks who have a sub-Saharan genetic profile, all Mediterranean populations depict a typical mediterranean substratum.     

High-resolution molecular characterization of the HLA class I and class II in the Tarahumara Amerindian population

We describe for the first time the high-resolution profiling of HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 in a culturally and geographically distinct Mexican ethnic group, the Tarahumaras. The alleles most frequently found by reference strand-mediated conformational analysis in this population were for class I: HLA-A*240201, *020101/09, *0206, *310102, *680102; HLA-B*4002, *1501, *510201, *3501/02/03, *4005, *4801; HLA-Cw*0304, *0801, *0102, *040101; and for class II: HLA-DRB1*080201, *1402, *040701; HLA-DQB1*0402, *0301, *0302/07; HLA-DPB1*0402, *0401, *020102. In addition, a novel allele, HLA-A*0257, was found. Based on comparison of presently known HLA-DRB1 and -DQB1 allele frequencies in Amerindian groups and worldwide populations, the Tarahumaras are unexpectedly more related to the geographically and linguistically distant Aymara and Terena Amerindian groups than they are to neighbouring tribes.     

Immunohistological characteristics of the infiltrating lymphoid cells and expression of HLA class I and II antigens in nasopharyngeal carcinoma

Summary The immunohistological characteristics of infiltrating lymphoid cells and the expression of human leucocyte antigens class I and II (HLA-ABC and HLA-DR, respectively) were studied in 50 pre-treatment nasopharyngeal carcinomas. The majority of lymphoid cells were activated lymphocytes expressing thymocyte OKT10 marker. CD4+ cells (T-helper/inducer) out-numbered CD8+ cells (T-suppressor/cytotoxic) by at least two-to four-fold. CD22+cells (pan-B lymphocytes) were scanty in the peri-tumoral areas and were absent in 29 out of 50 biopsies. A moderate number of cells expressing CD15 (monocytes/macrophages) were also detected. CD16+ cells (natural killer cells) were found to be sparse or absent. Expression of HLA class I and II antigens on the tumor cells in 35 biopsies was variable. HLA-ABC staining was intense in 6, reduced in 13 and partially lost in 16, whereas staining of HLADR was intense in 7, reduced in 11 and partially lost in 17. Full expression of both antigens was demonstrable in only 2 biopsy samples. The expression of HLA antigens in the tumour had no relationship to the type or degree of lymphocytic infiltration or staging of the tumour.     

Associations of Moyamoya patients with HLA class I and class II alleles in the Korean population

Moyamoya disease is characterized by progressive cerebrovascular occlusion at the peripheral internal carotid artery and development of abnormal collateral circulation at the cerebral basal region. Although abnormal thrombogenesis, inflammation and autoimmune process might be involved in the etiology, the genetic pathogenesis of Moyamoya disease is still unknown. To evaluate the association of Moyamoya disease with HLA alleles in the Korean population, we investigated HLA class I and class II alleles in 28 Moyamoya patients and 198 unrelated healthy controls. The frequency of HLA-B35 allele was significantly increased in the patients compared to the controls (32.1% vs. 10.1%, RR=4.2, p<0.008). Further analysis of HLA-B35 on onset age and sex showed that this allele was significantly increased compared to the controls in both late-onset and female group. Especially, HLA-B35 was the most significantly increased in female of late-onset group compared to the controls. These results suggest that HLA-B35 may be an useful genetic marker for Moyamoya disease, and particularly in females of late onset group in the Korean population.     

HLA class I polymorphism in the Cuban population

The extreme polymorphism found at some of the human leukocyte antigen (HLA) system loci makes it an invaluable tool for population genetic analyses. In the present study the genetic polymorphism of the Cuban population was estimated at HLA-A, -B, and -Cw loci by DNA typing. HLA class I allele and haplotype diversity were determined in 390 unrelated Cuban individuals (188 whites and 202 mulattos) from all over the country. In whites 19, 27, and 14 allele families for the HLA-A, -B, and -Cw loci, respectively, were identified. In mulattos, for the same loci, 20, 18, and 14 allele families were identified. Allele and haplotypes frequencies, comparisons with other worldwide populations based on genetic distances, neighbor-joining dendrograms, and correspondence analyses were estimated. Most of the identified allele groups and haplotypes are also common to sub-Saharan African and Europeans populations. However, Amerindian and Asian alleles were also detected at lower frequencies. The results clearly reveal the high diversity and interethnic admixture of the studied population. Our results provide useful information for the further studies of the Cuban population evolution and disease association in terms of HLA class I genes.     

HLA class I polymorphism in a Moroccan population from Casablanca

We have studied the distribution of HLA‐A and ‐B alleles and haplotypes by sequence‐specific primer amplification in a sample of 100 unrelated healthy individuals belonging to both Berber and Arabic‐speaking groups from the region of Casablanca in Morocco. Among the 17 HLA‐A and 23 HLA‐B alleles observed, the most frequent were HLA‐A2 (21%), ‐A1 (11%), ‐A3 (10%), ‐B44 (11.4%), ‐B50 (9.9%), ‐B5(8.5%) and ‐B35 (6.5%). Six two‐locus haplotypes were observed with a frequency above 5%: A2‐B50 (9.6%), A23‐B44 (7.4%), A2‐B15 (6.4%), A68‐B39 (5.3%), A1‐B51 (5.3%) and A68‐B44 (4.3%). Our data confirm that, on the basis of genetic distances, the majority of present‐day North Africans from Morocco are closely related to Berbers and also to Iberians. They cluster apart from Middle‐Eastern Mediterranean populations, and show greater genetic distances to Eastern and other Mediterranean populations. This study will serve as a reference for further anthropological studies, as well as studies of HLA and disease associations.     

HLA class I and class II genotyping in patients with Behcet's disease: a regional study of eastern part of Turkey

Class I human leucocyte antigen (HLA)-B51 is well known to be associated with Behcet's disease in many ethnic groups. However, there has been no published paper with respect to its association with HLA class I and class II among the Turkish people who live in the eastern region of Turkey. Moreover, as it is known that B51 antigen is encoded by 21 alleles, B*5101-5121, HLA-B51 allele typing was performed, as well as HLA class I and class II genotyping of 75 patients with the disease and the 54 individuals in the matched control group. The result shows that the HLA-B51 frequency was significantly higher (58.66%) in the patient group, compared to that in the control group (18.51%) (OR = 6.245). In the subtyping of B51 alleles, 44 B51-positive patients possessed B*5101 (45.5%), B*5108 (25%), B*5105 (9.1%) and B*5104 (4.5%). There was no significant difference in the HLA-B51 allelic distribution between the patient group and the control group. However, homozygous carriers of HLA-B51 showed considerably high risk (OR = 2.647) in the patient group, compared to that in the control group. In the genotyping of class II HLA alleles, while HLA-DRB1*04 (45.3%) and HLA-DRB1*07 (24%) were the predominant alleles in the patient group, DRB1*11 (50%) appeared to be more common in the control group.     

HLA class II molecular polymorphisms in healthy Slavic individuals from North-Western Russia

Polymerase chain reaction (PCR)-based genotyping was used to characterize the features of HLA class II molecular polymorphisms in a Slavic population of North-Western Russia. Two hundred individuals were analyzed for the DRB1 gene, and 100 persons randomly selected from this cohort were additionally typed for DQA1, DQB1 and DPB1 genes. Allele and haplotype frequencies were found to be similar to those observed in other Caucasian populations, with the exception of considerably high prevalence of the DPB1*0301 allele (16.0%) in the group studied. The high rate of diversity was observed within DRB1*04 and DRB1*14 specificities, as well as for extended DR-DQ haplotypes. In addition, significant number of "unusual" DR-DQ linkage patterns have been detected. The data seem to reflect the complexity of ethnic background of "European" Russians and may be helpful for the development of international network between donor registries.