التفاصيل البيبلوغرافية
| العنوان: |
HLA contributions to risk and protection for anti-centromere autoantibody-positive scleroderma |
| المؤلفون: |
Remmers, E F, Alexander, T, Morgan, N D, Shah, A A, Mayes, M D, Adeyemo, A, Doumatey, A, Bentley, A, Chandrasekharappa, S C, Carns, M A, Chung, L, Criswell, L A, Derk, C T, Domsic, R T, Gladue, H, Goldberg, A, Gordon, J K, Hsu, V, Jan, R, Khanna, D, Medsger, T A, Ramos, P S, Trojanowski, M, Saketkoo, L A, Schiopu, E, Shanmugam, W, Korman, B D, Kron, B, Bridges, S L, Kolstad, K D, Bernstein, E J, Kafaja, S, Maksimowicz-McKinnon, Kathleen, Silver, R, Steen, V D, Varga, J, Rotimi, C, Boin, F, Wigley, F M, Kastner, D L, Gourh, P |
| المصدر: |
Rheumatology Meeting Abstracts |
| بيانات النشر: |
Henry Ford Health Scholarly Commons |
| سنة النشر: |
2018 |
| المجموعة: |
Henry Ford Health System Scholarly Commons |
| الوصف: |
Background/Purpose: Anti-nuclear autoantibodies are a hallmark of scleroderma with anti-centromere antibody (ACA) recognizing centromeric antigens. ACA-positive patients have longstanding Raynaud's, limited cutaneous disease and increased risk for pulmonary arterial hypertension. We investigated the role of HLA classical genes and alleles on risk for ACA-positive scleroderma in a large collection of patients with scleroderma and genetically matched controls. Methods: SNP genotypes of 723 scleroderma cases and 5,561 controls, all of European ancestry, were obtained from dbGaP. Classical HLA types were imputed with SNP2HLA using the Type I Diabetes Genetic Consortium reference of 5,225 individuals. Association of HLA classical alleles was tested by a dominant model regression analysis coding the HLA types as numeric values (1 for present, 0 for absent). Regression tests were corrected for genetic dissimilarity by including the top 5 principal components as covariates. Results: Of the 723 scleroderma cases, 238 (32.9%) were positive for ACA. The most significantly ACA-positive scleroderma-associated HLA allele was HLA-DRB1∗07:01, which was disease protective (P-value=1.8x10-18, odds ratio (OR)=0.11 (95%CI=0.05 to 0.22)). This allele was found in only 3.4% of the ACA-positive cases versus 23.6% of controls and 20.8% of the ACA-negative cases. Regression analysis conditioning on the disease-associated alleles identified HLADQB1∗ 05:01 as the most significantly associated disease risk allele (P-value= 3.3x10-08, OR=2.18 (1.66-2.86)) with additional independent risk effects of HLA-DQA1∗04:01 and HLA-DQA1∗03:01). A two-locus analysis of the DQB1∗05:01 disease-risk and the DRB1∗07:01 disease-protective alleles suggested the risk effect of DQB1∗05:01 is overridden by the protective effect of DRB1∗07:01(Figure 1). The odds ratio for ACA-positive disease in individuals carrying both alleles was 0.14, similar to that in individuals carrying DRB1∗07:01 without DQB1∗05:01 (0.15). No effect of DRB1∗07:01 or DQB1∗05:01 was found ... |
| نوع الوثيقة: |
text |
| اللغة: |
unknown |
| Relation: |
https://scholarlycommons.henryford.com/rheumatology_mtgabstracts/1 |
| الاتاحة: |
https://scholarlycommons.henryford.com/rheumatology_mtgabstracts/1 |
| رقم الانضمام: |
edsbas.646CF6C3 |
| قاعدة البيانات: |
BASE |