Ena-DATASET-IC-06-10-2015-02:17:18:847-149 - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001001631 | EGA |
REPOSITORIES: EGA
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Project description:It is broadly accepted that psoriasis is an immune-mediated disease with a heritable component, but it is not clear what causes inflammation in the skin. Previous research suggests that fragments of the keratin 17 (K17) protein, which are constitutively expressed in hair follicles, could act as autoantigens. In this study, we synthesized the K17 protein from mRNA derived from hair follicles and tested whether it elicited T cell responses depending on the patient genotype at the major susceptibility locus HLA-Cw*06:02. We treated peripheral blood-derived cells with the K17 protein and its short fragments to assess the T cell proliferation response using flow cytometry. Our analyses show a significantly stronger increase in cell proliferation among patients but not in healthy controls. We then examined whether the variation in T cell proliferation correlated with the patient HLA-Cw*06:02 risk genotype. Considering the affected status and patient genotype as two independent predictors, we fitted a linear model and showed that the HLA-Cw*06:02 allele dosage strongly predicted the T cell response. Our study findings suggest that the K17 protein likely acts as an autoantigen in psoriasis and that patients' risk genotype is strongly correlated with the magnitude of the response to this putative autoantigen.
| S-EPMC5904118 | biostudies-literature
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| EGAD00001003280 | EGA
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| EGAD00001008199 | EGA
Project description:Essential hypersomnia (EHS), a sleep disorder characterized by excessive daytime sleepiness, can be divided into two broad classes based on the presence or absence of the HLA-DQB1*06:02 allele. HLA-DQB1*06:02-positive EHS and narcolepsy with cataplexy are associated with the same susceptibility genes. In contrast, there are fewer studies of HLA-DQB1*06:02 negative EHS which, we hypothesized, involves a different pathophysiological pathway than does narcolepsy with cataplexy. In order to identify susceptibility genes associated with HLA-DQB1*06:02 negative EHS, we conducted a genome-wide association study (GWAS) of 125 unrelated Japanese EHS patients lacking the HLA-DQB1*06:02 allele and 562 Japanese healthy controls. A comparative study was also performed on 268 HLA-DQB1*06:02 negative Caucasian hypersomnia patients and 1761 HLA-DQB1*06:02 negative Caucasian healthy controls. We identified three SNPs that each represented a unique locus- rs16826005 (P = 1.02E-07; NCKAP5), rs11854769 (P = 6.69E-07; SPRED1), and rs10988217 (P = 3.43E-06; CRAT) that were associated with an increased risk of EHS in this Japanese population. Interestingly, rs10988217 showed a similar tendency in its association with both HLA-DQB1*06:02 negative EHS and narcolepsy with cataplexy in both Japanese and Caucasian populations. This is the first GWAS of HLA-DQB1*06:02 negative EHS, and the identification of these three new susceptibility loci should provide additional insights to the pathophysiological pathway of this condition.
| S-EPMC3642778 | biostudies-literature
Project description:Peanut allergy (PA) is a common and serious food allergy and its prevalence has increased in the past decade. Although there is strong evidence of inheritance, the genetic causes of this disease are not well understood. Previously, a large-scale genome-wide association study described an association between human leukocyte antigen (HLA)-DQB1 and asthma; the aim of this study was to evaluate the association between HLA-DQB1 and PA. Genotypic and allelic profiles were established for 311 Caucasian members of a well-described Canadian group of children with PA and 226 Caucasian controls. Firth's logistic regression analyses showed associations between HLA-DQB1 alleles and PA for DQB1*02 (P=1.1 × 10(-8), odds ratio (OR)=0.09 (CI=0.03-0.23)) and DQB1*06:03P alleles (P=2.1 × 10(-2), OR=2.82 (CI=1.48-5.45)). This study of HLA in PA demonstrates specific association between two allelic groups of the HLA-DQB1 gene (DQB1*02 and DQB1*06:03P) and PA, highlighting its possible role in the development of this disease.
| S-EPMC3778350 | biostudies-literature
Project description:The association of narcolepsy-cataplexy, a sleep disorder caused by the loss of hypocretin/orexin neurons in the hypothalamus, with DQA1*01:02-DQB1*06:02 is one of the tightest known single-allele human leukocyte antigen (HLA) associations. In this study, we explored genome-wide expression in peripheral white blood cells of 50 narcolepsy versus 47 controls (half of whom were DQB1*06:02 positive) and observed the largest differences between the groups in the signal from HLA probes. Further studies of HLA-DQ expression (mRNA and protein in a subset) in 125 controls and 147 narcolepsy cases did not reveal any difference, a result we explain by the lack of proper control of allelic diversity in Affymetrix HLA probes. Rather, a clear effect of DQB1*06:02 allelic dosage on DQB1*06:02 mRNA levels (1.65-fold) and protein (1.59-fold) could be demonstrated independent of disease status. These results indicate that allelic dosage is transmitted into changes in heterodimer availability, a phenomenon that may explain the increased risk for narcolepsy in DQB1*06:02 homozygotes versus heterozygotes.
| S-EPMC3501142 | biostudies-literature
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| S-EPMC4366324 | biostudies-literature
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| EGAD00001006204 | EGA