BACKGROUND: Biopharmaceutical products (BPs) are widely used to treat autoimmune diseases, but immunogenicity limits their efficacy for an important proportion of patients. Our knowledge of patient-related factors influencing the occurrence of antidrug antibodies (ADAs) is still limited. METHODS AND FINDINGS: The European consortium ABIRISK (Anti-Biopharmaceutical Immunization: prediction and analysis of clinical relevance to minimize the RISK) conducted a clinical and genomic multicohort prospective study of 560 patients with multiple sclerosis (MS, n = 147), rheumatoid arthritis (RA, n = 229), Crohn's disease (n = 148), or ulcerative colitis (n = 36) treated with 8 different biopharmaceuticals (etanercept, n = 84; infliximab, n = 101; adalimumab, n = 153; interferon [IFN]-beta-1a intramuscularly [IM], n = 38; IFN-beta-1a subcutaneously [SC], n = 68; IFN-beta-1b SC, n = 41; rituximab, n = 31; tocilizumab, n = 44) and followed during the first 12 months of therapy for time to ADA development. From the bioclinical data collected, we explored the relationships between patient-related factors and the occurrence of ADAs. Both baseline and time-dependent factors such as concomitant medications were analyzed using Cox proportional hazard regression models. Mean age and disease duration were 35.1 and 0.85 years, respectively, for MS; 54.2 and 3.17 years for RA; and 36.9 and 3.69 years for inflammatory bowel diseases (IBDs). In a multivariate Cox regression model including each of the clinical and genetic factors mentioned hereafter, among the clinical factors, immunosuppressants (adjusted hazard ratio [aHR] = 0.408 [95% confidence interval (CI) 0.253-0.657], p < 0.001) and antibiotics (aHR = 0.121 [0.0437-0.333], p < 0.0001) were independently negatively associated with time to ADA development, whereas infections during the study (aHR = 2.757 [1.616-4.704], p < 0.001) and tobacco smoking (aHR = 2.150 [1.319-3.503], p < 0.01) were positively associated. 351,824 Single-Nucleotide Polymorphisms (SNPs) and 38 imputed Human Leukocyte Antigen (HLA) alleles were analyzed through a genome-wide association study. We found that the HLA-DQA1*05 allele significantly increased the rate of immunogenicity (aHR = 3.9 [1.923-5.976], p < 0.0001 for the homozygotes). Among the 6 genetic variants selected at a 20% false discovery rate (FDR) threshold, the minor allele of rs10508884, which is situated in an intron of the CXCL12 gene, increased the rate of immunogenicity (aHR = 3.804 [2.139-6.764], p < 1 × 10-5 for patients homozygous for the minor allele) and was chosen for validation through a CXCL12 protein enzyme-linked immunosorbent assay (ELISA) on patient serum at baseline before therapy start. CXCL12 protein levels were higher for patients homozygous for the minor allele carrying higher ADA risk (mean: 2,693 pg/ml) than for the other genotypes (mean: 2,317 pg/ml; p = 0.014), and patients with CXCL12 levels above the median in serum were more prone to develop ADAs (aHR = 2.329 [1.106-4.90], p = 0.026). A limitation of the study is the lack of replication; therefore, other studies are required to confirm our findings. CONCLUSION: In our study, we found that immunosuppressants and antibiotics were associated with decreased risk of ADA development, whereas tobacco smoking and infections during the study were associated with increased risk. We found that the HLA-DQA1*05 allele was associated with an increased rate of immunogenicity. Moreover, our results suggest a relationship between CXCL12 production and ADA development independent of the disease, which is consistent with its known function in affinity maturation of antibodies and plasma cell survival. Our findings may help physicians in the management of patients receiving biotherapies.
- MeSH
- adalimumab terapeutické užití MeSH
- autoimunitní nemoci farmakoterapie genetika MeSH
- biologická terapie metody MeSH
- biologické přípravky imunologie terapeutické užití MeSH
- celogenomová asociační studie metody MeSH
- Crohnova nemoc farmakoterapie genetika MeSH
- dospělí MeSH
- HLA-DQ alfa řetězec genetika MeSH
- humanizované monoklonální protilátky terapeutické užití MeSH
- imunosupresiva terapeutické užití MeSH
- infliximab terapeutické užití MeSH
- interferon beta 1a terapeutické užití MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- prospektivní studie MeSH
- revmatoidní artritida farmakoterapie genetika MeSH
- rituximab terapeutické užití MeSH
- roztroušená skleróza farmakoterapie genetika MeSH
- ulcerózní kolitida farmakoterapie genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adalimumab MeSH
- biologické přípravky MeSH
- HLA-DQ alfa řetězec MeSH
- HLA-DQA1 antigen MeSH Prohlížeč
- humanizované monoklonální protilátky MeSH
- imunosupresiva MeSH
- infliximab MeSH
- interferon beta 1a MeSH
- rituximab MeSH
- tocilizumab MeSH Prohlížeč
Next-generation sequencing (NGS) is increasingly used in transplantation settings, but also as a method of choice for in-depth analysis of population-specific HLA genetic architecture and its linkage to various diseases. With respect to complex ethnic admixture characteristic for East Croatian population, we aimed to investigate class-I (HLA-A, -B, -C) and class-II (HLA-DRB1, -DQA1, -DQB1) HLA diversity at the highest, 4-field resolution level in 120 healthy, unrelated, blood donor volunteers. Genomic DNA was extracted and HLA genotypes of class I and DQA1 genes were defined in full-length, -DQB1 from intron 1 to 3' UTR, and -DRB1 from intron 1 to intron 4 (Illumina MiSeq platform, Omixon Twin algorithms, IMGT/HLA release 3.30.0_5). Linkage disequilibrium statistics, Hardy-Weinberg departures, and haplotype frequencies were inferred by exact tests and iterative Expectation-Maximization algorithm using PyPop 0.7.0 and Arlequin v3.5.2.2 software. Our data provide first description of 4-field allele and haplotype frequencies in Croatian population, revealing 192 class-I and class-II alleles and extended haplotypic combinations not apparent from the existing 2-field HLA reports from Croatia. This established reference database complements current knowledge of HLA diversity and should prove useful in future population studies, transplantation settings, and disease-associated HLA screening.
- MeSH
- běloši genetika MeSH
- dárci krve MeSH
- dospělí MeSH
- frekvence genu MeSH
- haplotypy MeSH
- HLA-A antigeny genetika MeSH
- HLA-B antigeny genetika MeSH
- HLA-C antigeny genetika MeSH
- HLA-DQ alfa řetězec genetika MeSH
- HLA-DQ beta řetězec genetika MeSH
- HLA-DRB1 řetězec genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- sekvenční analýza DNA MeSH
- vazebná nerovnováha MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- zdraví dobrovolníci pro lékařské studie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Chorvatsko MeSH
- Názvy látek
- HLA-A antigeny MeSH
- HLA-B antigeny MeSH
- HLA-C antigeny MeSH
- HLA-DQ alfa řetězec MeSH
- HLA-DQ beta řetězec MeSH
- HLA-DQA1 antigen MeSH Prohlížeč
- HLA-DQB1 antigen MeSH Prohlížeč
- HLA-DRB1 řetězec MeSH
Differential expression of HLA-DQA1 and HLA-DQB1 gene alleles was analysed in three different cell populations isolated from peripheral blood-B lymphocytes, monocytes and whole-blood cells. Interallelic differences in mRNA levels were observed: DQA1*03 alleles were among the most expressed in all cell types, whereas DQA1*05 alleles were least expressed in whole blood and monocytes and among the most expressed in B cells. For DQB1 gene, DQB1*06 group of alleles were the most expressed, and DQB1*02 group the least expressed within all cell populations examined. In comparison with the rest alleles, DQB1*06 and DQB1*05:02 alleles have higher expression in monocytes than in B cells, professional antigen-presenting cells. Cell type-specific regulation of expression was observed as well, with higher and more balanced expression of alleles in B lymphocytes compared to monocytes.
- Klíčová slova
- HLA class II, HLA-DQA1, HLA-DQB1, antigen presentation, gene expression, genetic polymorphism,
- MeSH
- alely MeSH
- B-lymfocyty imunologie metabolismus MeSH
- dospělí MeSH
- exprese genu * MeSH
- frekvence genu MeSH
- haplotypy MeSH
- HLA-DQ alfa řetězec genetika MeSH
- HLA-DQ beta řetězec genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- messenger RNA genetika MeSH
- mladý dospělý MeSH
- monocyty imunologie metabolismus MeSH
- orgánová specificita MeSH
- senioři MeSH
- zdraví dobrovolníci pro lékařské studie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- HLA-DQ alfa řetězec MeSH
- HLA-DQ beta řetězec MeSH
- HLA-DQA1 antigen MeSH Prohlížeč
- HLA-DQB1 antigen MeSH Prohlížeč
- messenger RNA MeSH
Type 1 diabetes (T1D) belongs among polygenic multifactorial autoimmune diseases. The highest risk is associated with human leucocyte antigen (HLA) class II genes, including HLA-DQA1 gene. Our aim was to investigate DNA methylation of HLA-DQA1 promoter alleles (QAP) and correlate methylation status with individual HLA-DQA1 allele expression of patients with T1D and healthy controls. DNA methylation is one of the epigenetic modifications that regulate gene expression and is known to be shaped by the environment.Sixty one patients with T1D and 39 healthy controls were involved in this study. Isolated DNA was treated with sodium bisulphite and HLA-DQA1 promoter sequence was amplified using nested PCR. After sequencing, DNA methylation of HLA-DQA1 promoter alleles was analysed. Individual mRNA HLA-DQA1 relative allele expression was assessed using two different endogenous controls (PPIA, DRA). We have found statistically significant differences in HLA-DQA1 allele 02:01 expression (PPIA normalization, Pcorr = 0·041; DRA normalization, Pcorr = 0·052) between healthy controls and patients with T1D. The complete methylation profile of the HLA-DQA1 promoter was gained with the most methylated allele DQA1*02:01 and the least methylated DQA1*05:01 in both studied groups. Methylation profile observed in patients with T1D and healthy controls was similar, and no correlation between HLA-DQA1 allele expression and DNA methylation was found. Although we have not proved significant methylation differences between the two groups, detailed DNA methylation status and its correlation with expression of each HLA-DQA1 allele in patients with T1D have been described for the first time.
- Klíčová slova
- DNA methylation, HLA class II genes, HLA-DQA1 promoter (QAP), mRNA expression, type 1 diabetes mellitus,
- MeSH
- diabetes mellitus 1. typu genetika MeSH
- dospělí MeSH
- frekvence genu MeSH
- genetická predispozice k nemoci MeSH
- genotyp MeSH
- HLA-DQ alfa řetězec genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- messenger RNA analýza MeSH
- metylace DNA * MeSH
- mladý dospělý MeSH
- promotorové oblasti (genetika) genetika MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- HLA-DQ alfa řetězec MeSH
- HLA-DQA1 antigen MeSH Prohlížeč
- messenger RNA MeSH
One hundred and eighty Czech individuals from the Czech Republic pop 3 were genotyped at the HLA-DRB1, -DQA1 and -DQB1 loci using sequence-specific primers PCR methods. HLA-DRB1, -DQA1 and -DQB1 genotypes are consistent with expected Hardy-Weinberg (HW) proportions. These genotype data are available in the Allele Frequencies Net Database under identifier AFND.
- Klíčová slova
- Czech population, DQA1, DQB1, DRB1, HLA alleles,
- MeSH
- alely MeSH
- frekvence genu MeSH
- genotyp * MeSH
- haplotypy MeSH
- HLA-DQ alfa řetězec genetika MeSH
- HLA-DQ beta řetězec genetika MeSH
- HLA-DRB1 řetězec genetika MeSH
- lidé MeSH
- populační genetika * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- Názvy látek
- HLA-DQ alfa řetězec MeSH
- HLA-DQ beta řetězec MeSH
- HLA-DRB1 řetězec MeSH
OBJECTIVES: Extensive polymorphism of HLA class II genes is not restricted to the coding region of the gene. It extends also to the linked promoter region, where it forms the basis for different levels of individual allele's expression. Differential expression of HLA class II alleles can shape an immune response and influence the risk of developing autoimmune disease. In addition to genetic variability, variation in epigenetic modifications, including DNA methylation, can be another cause of the uneven expression of individual alleles. We aimed to analyze the DNA methylation of promoter sequences and the levels of expression of individual DQA1 gene alleles, interallelic variation of these two characteristics and the relationship between them. METHODS: The 60 healthy donors included into study were HLA-DRB1, HLA-DQB1 and HLA-DQA1 genotyped using PCR-SSP. Genomic DNA was treated by sodium bisulfite and the target segment in the HLA-DQA1 gene promoter was PCR amplified. PCR product was cloned into Escherichia coli and individual clones were sequenced. Transcripts of individual DQA1 alleles in peripheral blood leukocytes were quantified by Real-Time PCR. RESULTS: In this study, we have described detailed DNA methylation profile of promoter area of DQA1 gene alleles. The overall promoter methylation is increased for DQA1*02:01 and DQA1*04:01 alleles, on the other side, DQA1*05:01 allele shows decreased methylation level. Our results suggest that there are only minor interindividual differences in DRA-normalized expression level of specific allele. Furthermore, expression levels of individual alleles followed DQA1*03>*01:03 (in DRB1*13-DQA1*01:03-DQB1*06:03 haplotype)>*01:01,*05:05, and DQA1*03>*02:01>*05:05 hierarchy. The statistically significantly most expressed allele, DQA1*03, comprises part of DQ8 molecule, which is commonly linked to autoimmune diseases. A clear relationship between promoter DNA methylation and mRNA expression level of the DQA1 gene could not be identified.
- Klíčová slova
- DNA methylation, DQA1, HLA class II, Polymorphism, mRNA expression,
- MeSH
- alely * MeSH
- CpG ostrůvky MeSH
- dospělí MeSH
- haplotypy MeSH
- HLA-DQ alfa řetězec genetika MeSH
- HLA-DQ beta řetězec genetika MeSH
- HLA-DRB1 řetězec genetika MeSH
- lidé MeSH
- messenger RNA genetika MeSH
- metylace DNA * MeSH
- mladý dospělý MeSH
- promotorové oblasti (genetika) * MeSH
- regulace genové exprese * MeSH
- zdraví dobrovolníci pro lékařské studie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- HLA-DQ alfa řetězec MeSH
- HLA-DQ beta řetězec MeSH
- HLA-DQA1 antigen MeSH Prohlížeč
- HLA-DQB1 antigen MeSH Prohlížeč
- HLA-DRB1 řetězec MeSH
- messenger RNA MeSH
Autoimmune diabetes mellitus, called type 1 diabetes mellitus (T1DM), is caused by autoimmune destruction of islet beta cells in the pancreas. T1DM susceptibility loci mapped by different genome screening are IDDM1-IDDM18. It has been estimated that HLA (IDDM1) provides up to 40-50 % of the familial clustering of T1DM (LOD score of 65.8). Many studies have verified that DQB1*0302 is a strong susceptibility gene and that the heterozygous combination of DQA1*0301-DQB1*0302 on the HLA-DR4 haplotype and DQA1*0501-DQB1*0201 on the HLA-DR3 haplotype results in a synergistically increased risk of T1DM. The presence of predisposing genes in autoimmune diabetes decreases with age, probably due to increasing influence of environmental factors. Autoimmune diabetes with manifestation in adults may have partly different immunogenetic etiopathogenesis than autoimmune diabetes with manifestation in childhood. Compared to fast progressing adult-onset T1DM, slowly progressing adult-onset type 1 diabetes (LADA) might involve genes leading to a slow progressive beta-cells destruction.
- MeSH
- autoimunita imunologie MeSH
- autoprotilátky imunologie MeSH
- diabetes mellitus 1. typu genetika imunologie MeSH
- dítě MeSH
- dospělí MeSH
- genetická predispozice k nemoci MeSH
- haplotypy MeSH
- HLA-DQ alfa řetězec MeSH
- HLA-DQ antigeny genetika MeSH
- HLA-DQ beta řetězec MeSH
- HLA-DR antigeny genetika MeSH
- HLA-DR3 antigen genetika MeSH
- HLA-DR4 antigen genetika MeSH
- lidé MeSH
- polymorfismus genetický MeSH
- progrese nemoci MeSH
- rizikové faktory MeSH
- věkové faktory MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- srovnávací studie MeSH
- Názvy látek
- autoprotilátky MeSH
- HLA-DQ alfa řetězec MeSH
- HLA-DQ antigeny MeSH
- HLA-DQ beta řetězec MeSH
- HLA-DQA1 antigen MeSH Prohlížeč
- HLA-DQB1 antigen MeSH Prohlížeč
- HLA-DR antigeny MeSH
- HLA-DR3 antigen MeSH
- HLA-DR4 antigen MeSH
Host-pathogen interactions are of particular interest in studies of the interplay between population dynamics and natural selection. The major histocompatibility complex (MHC) genes of demographically fluctuating species are highly suitable markers for such studies, because they are involved in initiating the immune response against pathogens and display a high level of adaptive genetic variation. We investigated whether two MHC class II genes (DQA1, DRB) were subjected to contemporary selection during increases in the density of fossorial water vole (Arvicola terrestris) populations, by comparing the neutral genetic structure of seven populations with that estimated from MHC genes. Tests for heterozygosity excess indicated that DQA1 was subject to intense balancing selection. No such selection operated on neutral markers. This pattern of selection became more marked with increasing abundance. In the low-abundance phase, when populations were geographically isolated, both overall differentiation and isolation-by-distance were more marked for MHC genes than for neutral markers. Model-based simulations identified DQA1 as an outlier (i.e. under selection) in a single population, suggesting the action of local selection in fragmented populations. The differences between MHC and neutral markers gradually disappeared with increasing effective migration between sites. In the high-abundance year, DQA1 displayed significantly lower levels of overall differentiation than the neutral markers. This gene therefore displayed stronger homogenization than observed under drift and migration alone. The observed signs of selection were much weaker for DRB. Spatial and temporal fluctuations in parasite pressure and locus-specific selection are probably the most plausible mechanisms underlying the observed changes in selection pattern during the demographic cycle.
- MeSH
- Arvicolinae genetika MeSH
- frekvence genu MeSH
- genetická variace MeSH
- genotyp MeSH
- geny MHC třídy II genetika MeSH
- HLA-DQ alfa řetězec MeSH
- HLA-DQ antigeny genetika MeSH
- HLA-DR antigeny genetika MeSH
- hustota populace MeSH
- mikrosatelitní repetice genetika MeSH
- molekulární sekvence - údaje MeSH
- populační genetika MeSH
- sekvenční analýza DNA MeSH
- selekce (genetika) * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- HLA-DQ alfa řetězec MeSH
- HLA-DQ antigeny MeSH
- HLA-DQA1 antigen MeSH Prohlížeč
- HLA-DR antigeny MeSH
OBJECTIVE: The overlap between genetic susceptibility to celiac disease (CD) and to type 1 diabetes is incomplete; therefore, some genetic polymorphisms may significantly modify the risk of CD in subjects with type 1 diabetes. This study aimed to investigate whether the susceptibility to CD in diabetic children is modified by positivity for HLA-DQB1*02-DQA1*05 and DQB1*0302-DQA1*03 and by alleles of single nucleotide polymorphisms within the genes encoding CTLA4, transforming growth factor (TGF)-beta, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-1, IL-2, IL-6, and IL-10. RESEARCH DESIGN AND METHODS: Genotypic data were compared between 130 case subjects (children with type 1 diabetes and CD diagnosed using endomysium antibodies) and 245 control subjects (children with type 1 diabetes only, optimally two per case, matched for center, age at type 1 diabetes onset, and type 1 diabetes duration). The subjects were recruited from 10 major European pediatric diabetes centers performing regular screening for CD. The polymorphisms were determined using PCR with sequence-specific primers, and the risk was assessed by building a step-up conditional logistic regression model using variables that were significantly associated with CD in the univariate analysis. RESULTS: The best-fitted model showed that risk of CD is increased by presence of HLA-DQB1*02-DQA1*05 (odds ratio 4.5 [95% CI 1.8-11], for homozygosity, and 2.0 [1.1-3.7], for a single dose) and also independently by TNF -308A (1.9 [1.1-3.2], for phenotypic positivity), whereas IL1-alpha -889T showed a weak negative association (0.6 [0.4-0.9]). CONCLUSIONS: The results indicate that the risk of CD in children with type 1 diabetes is significantly modified both by the presence of HLA-DQB1*02-DQA1*05 and by a variant of another gene within the major histocompatibility complex, the TNF -308A.
- MeSH
- celiakie komplikace genetika imunologie MeSH
- diabetes mellitus 1. typu komplikace genetika imunologie MeSH
- dítě MeSH
- fenotyp MeSH
- genetická predispozice k nemoci MeSH
- genotyp MeSH
- HLA-DQ alfa řetězec MeSH
- HLA-DQ antigeny genetika MeSH
- HLA-DQ beta řetězec MeSH
- lidé MeSH
- mladiství MeSH
- regresní analýza MeSH
- rizikové faktory MeSH
- studie případů a kontrol MeSH
- TNF-alfa genetika MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- Názvy látek
- HLA-DQ alfa řetězec MeSH
- HLA-DQ antigeny MeSH
- HLA-DQ beta řetězec MeSH
- HLA-DQA1 antigen MeSH Prohlížeč
- HLA-DQB1 antigen MeSH Prohlížeč
- TNF-alfa MeSH
OBJECTIVES: Several associations between HLA complex and diabetes mellitus type IA were found in various groups of patients of Caucasoid population. This study was therefore prompted to be conducted in Slovak population, since any such has not yet been performed in Slovak population. METHODS: Patients suffering from DM-1A originated from all regions of Slovakia. Their age ranged from 1 to 42 years; but the criterion for including the subject to the study was the definition of diagnosis in older patients before their age of 15 (Table 1). The diagnosis was set up according to internationally accepted criteria. A total of 460 patients was typed for HLA-DQB1 alleles, among them 97 also for HLA-DQA1 and 146 for HLA-DRB1 alleles. HLA-typing was performed by a PCR-SSP method. Control group consisted of 196 (DQA), 143 (DQB1) and 130 (DRB1) unrelated blood donors aged 19-55 years old irrespective of their age or sex. The data obtained were expressed in a 2 x 2 contingency table and statistical significance was calculated by the Fisher exact test. RESULTS: Among 11 HLA-DQB1 alleles tested DOB1*0302 was the most frequent in DM-1A patients (30.33% vs. 5.59% in healthy subjects (HS), followed by DQB1*0201 (22.93% vs. 12.94%, respectively). In contrast, the frequency rate of DQB1*0301 (10.66% vs. 24.48%), DOB1*0602 (2.17% vs. 10.14%) and DQB1*0603 (2.5% vs. 8.39 %) were decreased in DM-1A patients. Out of 14 DQA1 alleles the highest occurrence rate showed DQA1*0301 (30.93% vs. 17.09) and DQA1*0501 (34.02% vs. 25.76%), while DQA1*0102 (8.76% vs. 16.58%) and DQA1*0201 (6.18 % vs. 13.51%7), respectively, were found to be the least frequent. Among 13 HLA-DRB1 alleles tested, the most common occurrence rates showed DRB1*03 (26.37% vs. 9.62%) and DRB1*04 (7.19% vs. 14.23%), while the least frequent alleles were DRB 1*15 (2.74% vs. 12.31%), DRB1*07 (7.19% vs. 14.23%), and DRB1*11 (2.74% vs. 20.38%). The alleles DQB1*0302 and DQA1*0301, respectively, were present in the same individual in all DRB1*04 positive patients, suggesting that they belong to the haplotype. Similar situation was observed with the alleles DQB1*0201, DQA1*0501, and DRB*0301, respectively, forming the second HLA haplotype so characteristic for DM1A.
- MeSH
- diabetes mellitus 1. typu genetika imunologie MeSH
- dítě MeSH
- dospělí MeSH
- frekvence genu * MeSH
- genetická predispozice k nemoci MeSH
- genetická vazba MeSH
- geny MHC třídy II * MeSH
- HLA-D antigeny klasifikace genetika MeSH
- HLA-DQ alfa řetězec MeSH
- HLA-DQ antigeny genetika MeSH
- HLA-DQ beta řetězec MeSH
- HLA-DR antigeny genetika MeSH
- HLA-DRB1 řetězec MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- předškolní dítě MeSH
- referenční hodnoty MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Geografické názvy
- Slovenská republika MeSH
- Názvy látek
- HLA-D antigeny MeSH
- HLA-DQ alfa řetězec MeSH
- HLA-DQ antigeny MeSH
- HLA-DQ beta řetězec MeSH
- HLA-DQA1 antigen MeSH Prohlížeč
- HLA-DQB1 antigen MeSH Prohlížeč
- HLA-DR antigeny MeSH
- HLA-DRB1 řetězec MeSH