Comparison of HLA class II antigens between three type 1 diabetes groups in the central region of Algeria : research article
Rachida RaacheAmel BenyahiaHabiba AmrounNadine AttalW. HamianeM. AzzouzL. LacetSimone Elisabeth HaworthA. BoudibaM.C. Abbadi
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Abstract:
In human type 1 diabetes (T1D), both genetic and environmental factors are involved in the pathogenesis of the disease. The strongest genetic contribution has been mapped to the major histocompatibility complex (MHC) on the short arm of chromosome 6, which encodes the human leukocyte antigens (HLA). It is estimated that HLA class II gene polymorphisms account for 20 to 50% of familial aggregation of type 1 diabetes. Several studies have clearly demonstrated that there are susceptibility and protective markers at HLA-DR and -DQ.
In this study, HLA class II antigens were investigated using a serological method in 210 T1D patients from the central region of Algeria, and compared to 140 healthy controls. Marker frequencies were compared between three groups of diabetics : children, juveniles and adults with latent autoimmune diabetes (LADA), and the control group.
The frequency was calculated for HLA-DR and -DQ. Significant differences were detected between T1D patient and the control groups for the frequencies of HLA-DR3, -DR4, -DQ2 and -DQ8 (DQ3) but there were no significant differences in these antigen frequencies between the three T1D groups versus the controls, with the respective frequencies of HLA-DR3 (71.76, 66.67, 70% vs 31.43%), HLA-DR4 (64.71, 48.89, 52.50% vs 26.43%), HLA-DQ2 (76.47, 66.67, 75% vs 39.29%) and HLA-DQ8 (3) (64.71, 46.67, 47.50% vs 19.29%).
Mantel-Haenszel tests were used to calculate the odds ratio for the presence of type 1 diabetes in association with HLA-DR3, -DR4, -DQ2 and -DQ8 (3). The values for each respective HLA antigen were as follows : for the T1D children (OR: 5.54; 5.1; 5.02; 7.67) for the juveniles (OR: 4.36; 2.66; 3.09; 3.66) and for LADA (OR: 5.09; 3.08; 4.64; 3.79). The heterozygous phenotype HLA-DR3/DR4 increased the risk (conferred the highest susceptibility) (OR: 8.79, 2.68, 4.23 for children, juveniles and the LADA group, respectively).
These results confirm the positive association between T1D and HLA class II antigens, as previously reported in other populations in the central region of Algeria.Keywords:
HLA-DQ
Histocompatibility
Pathogenesis
Genetic predisposition
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A strong genetic association between celiac disease (CD) and the human leukocyte antigen (HLA) has been widely demonstrated. In Europe, the HLA-DQ2 allele is predominant. However, studies in Latin America indicate that HLA-DQ8 could be more frequent. In Mexico, the frequency of those alleles has not been reported in subjects with CD. Therefore, the aim of the present study was to evaluate the distribution of HLA-DQ2 and HLA-DQ8 in Mexican individuals with CD. An exploratory study was conducted on a cohort of 49 subjects with chronic diarrhea. Autoantibodies for CD, duodenal atrophy, and HLA haplotypes were determined. Thirty individuals had CD (23 women, mean age 54.2 ± 15.5 years), 24 (80%) of whom expressed HLA-DQ8, 15 (50%) expressed HLA-DQ2, and 11 (37%) presented with both alleles. However, neither the HLA-DQ2 nor the HLA-DQ8 allele was found in 5 (10%) individuals. In subjects with chronic diarrhea that did not have CD, 12 (63%) presented with HLA-DQ2, and 7 (37%) with HLA-DQ8. Individuals with CD expressed the combinations of the HLA-DQ8/DQ2 alleles (37 vs. 5%) and the HLA-DR4/DQ8 alleles (60 vs. 26%) more frequently than the subjects without CD. In Mexican subjects with CD, HLA-DQ8 distribution was more frequent than that of HLA-DQ2, indicating a possible similarity to the frequency reported in other Latin American countries. However, given the nature of the present study and its sample size, further conclusions could not be reached. Existe una fuerte asociación entre la enfermedad celiaca (EC) y el antígeno leucocitario humano (HLA). En Europa predomina el alelo HLA-DQ2; sin embargo, estudios en América Latina indican que el HLA-DQ8 podría ser más frecuente. En México no se ha reportado la frecuencia de estos alelos en sujetos con EC. Por lo tanto, el objetivo de nuestro estudio fue determinar la distribución de HLA-DQ2 y HLA-DQ8 en sujetos mexicanos con EC. Se llevó a cabo un estudio exploratorio con una cohorte de 49 individuos, en quienes se buscó la presencia de marcadores serológicos, histológicos y genéticos de la EC. Treinta sujetos (23 mujeres) con una edad promedio de 54.2 ± 15.5 años presentaron EC; 24 (80%) de ellos expresaron HLA-DQ8 y 15 (50%) HLA-DQ2; 11 (37%) presentaron ambos alelos; sin embargo, en 5 (10%) individuos no se encontró HLA-DQ2 ni HLA-DQ8. Entre los sujetos con diarrea crónica que no tuvieron EC, 12 (63%) presentaron HLA-DQ2 y 7 (37%) HLA-DQ8. Los sujetos con EC expresaron más frecuentemente la combinación de HLA-DQ8/DQ2 (37% vs. 5%) y los alelos HLA-DR4/DQ8 (60% vs. 26%). En sujetos mexicanos con EC la expresión de HLA-DQ8 fue más frecuente que la de HLA-DQ2, lo cual indica que la distribución de HLA podría ser similar a las descritas en otros países de América Latina. Sin embargo, la naturaleza y el tamaño de la muestra de este estudio no permiten hacer más conclusiones.
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Objective:To test whether some pertiawar HLA class Ⅱ DR and DQ allelic polymorphism is associated with all kinds of chronic diseases in Chinese population.Methods:The DNA samples of Chinese patients with chronic diseases including cirrhosis of the liver,HBsAg carrier,glaucoma,nasal polyps,schizophrenia,cataract,AIDS and chronic renal failure were from different research group in Dalian Medical University.Fifteen samples were selected randomly in each of 8 diseases.One hundred twenty samples were taken.The control group was 80 healthy blood donors from the same geographical area.The samples were typed using an HLA-DR and HLA-DQ low resolution PCR-SSP typing kit.Results:The results showed that there was no statistical difference between two groups about allele frequencies of alleles for HLA-DR;Frequency of HLA-DQ9 was 14.58% in disease group as well as 6.25% in control group and significant difference was obtained ( P 0.05);No statistically significant difference in other alleles HLA-DQ frequency was noted in the disease group compared to that in control group.Conclusion:These results implied that on the same special HLA-DQ allele may be primarily associated with susceptibility to diseases and suggested that round regions of loci HLA-DQ may harbour diseases susceptibility genes.
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The association of HLA class II phenotype with the development of insulin-dependent (Type 1) diabetes mellitus (IDDM) is well established but the contribution of the various HLA-DR and -DQ alleles and haplotypes to disease predisposition is not fully understood. We have determined haplo- type and genotype odds ratios, and further employed multivariate tree analysis to explore the contribution of individual HLA-DRDQ haplotypes to the genetic risk for developing IDDM in the Dutch population. Next to haplotype and genotype odds ratios, multivariate tree analysis techniques provide overall risk calculations for each modeled parameter, and offer in- sight in the interaction of the model parameters via tree-shaped reports, in which subsequent stratifications on the data can easily be followed. We compared 206 Dutch IDDM patients with 840 serologically typed random healthy unrelated Dutch Caucasoid controls. The multivariate tree analysis showed that the HLA-DR7DQ9 and DR15DQ6 haplotype were strongly as- sociated with disease protection (OR50.04, P50.0003, and OR50.07, P5 ,0.0001, respectively). The highest ORs were found for the DR4DQ8/ DR8DQ4 genotype (OR521.04, P50.001), followed by DR4DQ8/DR17DQ2 (OR512.45, P, 0.0001) and DR9DQ9/DR17DQ2 (OR510.87, P50.02). DR4DQ8 homozygous and DR17DQ2 homozygous individuals have a dis- ease OR of 9.0 and 3.0 (P50.01 and 0.03), respectively. In conclusion, the results from haplotype, genotype, and tree analyses provide insight into the disease associations for combinations of HLA-DRDQ haplotypes. We con- firm that the DR9DQ9/DR17DQ2 genotype is associated with susceptibility in the Dutch population, which has previously been noticed as a HLA risk genotypes in Asian populations only. The human major histocompatibility complex (MHC), HLA, has been shown to be the major genetic component (IDDM1) associated with the development of diabetes mellitus type 1 (IDDM) (1-4). The strongest association is with the HLA-DQB1 locus, implying the highest genetic risk for the development of IDDM as well as protec- tion against this disease (5, 6). However, in recent years it has be- come evident that IDDM1 constitutes a joint interaction of DQB1, DQA1, and DRB1 (5, 7-12). Due to the strong linkage disequilibrium 2 ,
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In order to investigate the immunogenetic mechanism of Behçet's disease, frequencies of HLA antigens were studied in patients. The subjects consisted of 66 patients and 99 normal controls. A lymphocyte cytotoxicity test was used for typing HLA-A, -B, -C, -DR, -DQ antigens. HLA-DP antigens were analyzed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. A significant increase of HLA-B15 was observed in the patients. In contrast, no significant difference was observed in HLA-Bw52 which possesses only two different amino acids from HLA-B15. On the contrary, frequencies of HLA-A11, HLA-Aw33, HLA-B35, HLA-B44 and HLA-DQw1 were significantly lower in the patients than in the controls. No significant difference was observed in HLA-DP antigens. These results suggest that Behçet's disease involves both disease susceptibility factors and disease resistance factors and that such genetic factors are mapped within or very close to the HLA-B gene in the class I gene region. Additionally class II HLA-DQ antigen is associated with disease resistance factors.
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Abstract: The association of HLA class II phenotype with the development of insulin‐dependent (Type 1) diabetes mellitus (IDDM) is well established but the contribution of the various HLA‐DR and ‐DQ alleles and haplotypes to disease predisposition is not fully understood. We have determined haplotype and genotype odds ratios, and further employed multivariate tree analysis to explore the contribution of individual HLA‐DRDQ haplotypes to the genetic risk for developing IDDM in the Dutch population. Next to haplotype and genotype odds ratios, multivariate tree analysis techniques provide overall risk calculations for each modeled parameter, and offer insight in the interaction of the model parameters via tree‐shaped reports, in which subsequent stratifications on the data can easily be followed. We compared 206 Dutch IDDM patients with 840 serologically typed random healthy unrelated Dutch Caucasoid controls. The multivariate tree analysis showed that the HLA‐DR7DQ9 and DR15DQ6 haplotype were strongly associated with disease protection (OR=0.04, P =0.0003, and OR=0.07, P =<0.0001, respectively). The highest ORs were found for the DR4DQ8/DR8DQ4 genotype (OR=21.04, P =0.001), followed by DR4DQ8/DR17DQ2 (OR=12.45, P < 0.0001) and DR9DQ9/DR17DQ2 (OR=10.87, P =0.02). DR4DQ8 homozygous and DR17DQ2 homozygous individuals have a disease OR of 9.0 and 3.0 ( P =0.01 and 0.03), respectively. In conclusion, the results from haplotype, genotype, and tree analyses provide insight into the disease associations for combinations of HLA‐DRDQ haplotypes. We confirm that the DR9DQ9/DR17DQ2 genotype is associated with susceptibility in the Dutch population, which has previously been noticed as a HLA risk genotypes in Asian populations only.
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The aim of this study was to determine the frequency of HLA DR-DQ haplotypes in children with type 1 diabetes mellitus (T1DM) in the Southeast Region of Turkey.Eighty children and adolescents with T1DM and eighty control subjects participated in the study. HLA-DR, DQ was typed using polymerase chain reaction and sequence-specific priming technique.HLA DRB1*03 allele was significantly more common in patients than in control subjects. HLA DRB1*11, HLA DRB1*13 and HLA DRB1*14 allele frequencies were significantly lower in patients than in controls. DQB1*02 allele was more common in patients, whereas DQB1*03 allele was more frequent in control subjects. HLA DRB1*03-DQB1*02 haplotype was more frequently observed among patients.These results confirm the similar potential trends in the frequency distribution of HLA susceptibility genes with T1DM previously observed in Turkey and in other Caucasian populations.
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Introduction Class II HLA antigens were investigated in a group of 28 patients with insulin-dependent diabetes mellitus (IDDM) and 218 healthy unrelated persons (control group) from Vojvodina. Material and methods We used a modified two-colour immunofluorescence method (serologic technique) to determine the phenotype of DR and DQ locus HLA antigens. Phenotype frequencies of class II HLA antigens were determined in both investigated groups and were used for calculating relative risk (RR). If RR was higher than 1, we calculated the population attributable risk (EF), and if RR was lower than 1, we calculated the preventive fraction (PF). Investigation of statistically significant differences in frequencies of class II HLA antigens in patients and control group was performed by using ?2 test. Results Results of investigation showed that values of RR were higher than 1 for HLA DR4 (2,808), DR10 (1,116) and DQ3 (1,386), while we noticed a statistically significant difference in frequencies of HLA DR4 (?2 test: 4,805) in patients regarding control group. HLA DQ1 antigen has a preventive role in development of IDDM due to highest value of PF (0,314). Conclusion Results of our investigation confirm that there is an association of HLA DR4 with IDDM in population of Vojvodina. High values of relative risk of IDDM, noticed in persons with HLA DR4 antigen, point to the degree of risk of IDDM, which is a disease with great socioeconomic importance in Vojvodina.
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Objective The relationship between LADA and HLA-DQ and DR genes was studied. Methods The genotypes of HLA-DR and DQ in 60 healthy controls, 41 patients with type 1 diabetes, 39 patients with LADA were determined by PCR-SSP. Result (1)HLA-DR3,DR4,HLA-DQA1*0301,DQB1*0201 were positively associated with type 1 diabetes; HLA-DR15, HLA-DQB1*0601 were negatively associated with type 1 diabetes.(2)The frequencies of HLA-DR4,HLA-DQ*0301,HLA-DQB1*0201 were positively associated with LADA,and the frequencies of HLA-DQB1*0601 were significantly higher in LADA group than those in type 1 diabetic group. Conclusion Different genetic background may influence the progression of LADA and type 1 diabetes.
Autoimmune diabetes
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The distribution of HLA class-I (A, B and C), and class II (DR and DQ) antigens was studied in 50 randomly selected Kashmiri Muslim patients with established rheumatic heart disease and compared with that of 50 controls of similar ethnicity. A significant increase in the frequency of HLA-DR4 (P < 0.005, RR 3.27) and a significant decrease in the frequency of HLA-B5 (P < 0.001, RR 0.19) were found in the patient group. Though HLA-DQ3 showed a significant increase (P < 0.005, RR 2.52) and HLA-DR7 a significant decrease (P < 0.05, RR 0.42) in the patient group, the corrected P value was not significant. The findings suggest that susceptibility to RHD in the studied population is HLA-related, with HLA-DR4 influencing its occurrence and HLA-B5 conferring protection against the same.
Kashmiri
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