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DR Loci (dr + locus)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Long-term outcome of human leukocyte antigen mismatching in liver transplantation: Results of the national institute of diabetes and digestive and kidney diseases liver transplantation database,,

HEPATOLOGY, Issue 3 2008
Vijayan Balan
A perfect or nearly perfect human leukocyte antigen (HLA) match has been associated with better immediate and long-term survival of diseased donor kidney transplants. However, the effect of HLA matching for hepatic allografts remains poorly defined. Using data from the National Institutes of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database, we investigated the association between HLA mismatches and hepatic allograft survival, disease recurrence, and immunosuppression interactions. A, B, and DR loci were used to calculate total mismatch scores of 0 (no mismatches in any loci) to 6 (mismatches in all loci). Seven hundred ninety-nine adults (male, 55%; female, 45%) underwent 883 liver transplants. The 10-year graft survival according to total mismatch score was as follows: 0-2, 60%; 3-4, 54%; and 5-6, 57%. There was a negative effect of mismatching at the A locus on patient survival, with shorter survival for patients with 1 or 2 mismatches compared with 0 mismatches [P = 0.05, hazard ratio (HR) = 1.6]. Patients on tacrolimus with 1 or 2 mismatches at B or DR loci appeared to have increased rates of patient and graft survival compared to patients with 0 mismatches, with the appearance of a protective effect of tacrolimus (HR = 0.67). The effect of HLA mismatching was more pronounced on certain disease recurrences. DR-locus mismatch increased recurrence of autoimmune hepatitis (P = 0.01, HR = 4.2) and primary biliary cirrhosis (P = 0.04, HR = 2). Mismatch in the A locus was associated with more recurrence of hepatitis C virus (P = 0.01, HR = 1.6) and primary sclerosing cholangitis (P = 0.03, HR = 2.9). Conclusion: Mismatching at the A locus decreases patient survival in liver transplant recipients, and mismatching at the DR and A loci affects recurrence of autoimmune liver diseases and hepatitis C, respectively. (HEPATOLOGY 2008.) [source]

HLA,DRB4 as a genetic risk factor for Churg-Strauss syndrome

ARTHRITIS & RHEUMATISM, Issue 9 2007
Augusto Vaglio
Objective To explore the association between HLA alleles and Churg-Strauss syndrome (CSS), and to investigate the potential influence of HLA alleles on the clinical spectrum of the disease. Methods Low-resolution genotyping of HLA,A, HLA,B, and HLA,DR loci and genotyping of TNFA ,238A/G and TNFA ,308A/G single-nucleotide polymorphisms were performed in 48 consecutive CSS patients and 350 healthy controls. Results The frequency of the HLA,DRB1*07 allele was higher in the CSS patients than in controls (27.1% versus 13.3%; ,2 = 12.64, P = 0.0003, corrected P [Pcorr] = 0.0042, odds ratio [OR] 2.42, 95% confidence interval [95% CI] 1.47,3.99). The HLA,DRB4 gene, present in subjects carrying either HLA,DRB1*04, HLA,DRB1*07, or HLA,DRB1*09 alleles, was also far more frequent in patients than in controls (38.5% versus 20.1%; ,2 = 16.46, P = 0.000058, Pcorr = 0.000232, OR 2.49, 95% CI 1.58,3.09). Conversely, the frequency of the HLA,DRB3 gene was lower in patients than in controls (35.4% versus 50.4%; ,2 = 7.62, P = 0.0057, Pcorr = 0.0228, OR 0.54, 95% CI 0.35,0.84). CSS has 2 major clinical subsets, antineutrophil cytoplasmic antibody (ANCA),positive, with features of small-vessel vasculitis, and ANCA-negative, in which organ damage is mainly mediated by tissue eosinophilic infiltration; analysis of HLA,DRB4 in patients categorized by different numbers of vasculitic manifestations (purpura, alveolar hemorrhage, mononeuritis multiplex, rapidly progressive glomerulonephritis, and constitutional symptoms) showed that its frequency strongly correlated with the number of vasculitis symptoms (P for trend = 0.001). Conclusion These findings indicate that HLA,DRB4 is a genetic risk factor for the development of CSS and increases the likelihood of development of vasculitic manifestations of the disease. [source]

Microbiological, immunological and genetic factors in family members with periodontitis as a manifestation of systemic disease, associated with hematological disorders

JOURNAL OF PERIODONTAL RESEARCH, Issue 4 2002
Mitsugi Okada
The microflora, immunological profiles of host defence functions, and human leukocyte antigen (HLA) findings are reported for a mother, son and daughter who were diagnosed as having ,periodontitis as a manifestation of systemic diseases, associated with hematological disorders'. Examinations were made of the bacterial flora from the periodontal pocket, neutrophil chemotaxis, neutrophil phagocytosis, and the genotypes (DQB1) and serotypes (DR locus) of HLA class II antigens. Phenotypic analyses of the peripheral lymphocytes were also conducted. The subgingival microflora from the mother was dominated by Gram-negative rods, especially Porphyromonas endodontalis, Prevotella intermedia/Prevotella nigrescens and Fusobacterium nucleatum. Subgingival microflora samples from the son and daughter were dominated by Gram-positive cocci and Gram-positive rods. Through the use of polymerase chain reaction, Campylobacter rectus and Capnocytophaga gingivalis were detected in all subjects, whereas Porphyromonas gingivalis, P. intermedia, and Treponema denticola were not detected in any subjects. All three subjects showed a remarkable level of depressed neutrophil chemotaxis to N-formyl-methionyl-leucyl-phenylalanine, although their phagocyte function levels were normal, in comparison to healthy control subjects. Each subject had the same genotype, HLA-DQB1*0601, while the mother had HLA-DR2 and HLA-DR8, and the son and daughter had HLA-DR2 only. In summary, the members of this family showed a similar predisposition to periodontitis with regard to certain host defence functions. It is suggested that the depressed neutrophil chemotaxis that was identified here could be a significant risk factor for periodontitis in this family. [source]

Testing for Genetic Association in the Presence of Linkage and Gene,Covariate Interactions

BIOMETRICAL JOURNAL, Issue 1 2010
Andrea Callegaro
Abstract In order to study family-based association in the presence of linkage, we extend a generalized linear mixed model proposed for genetic linkage analysis (Lebrec and van Houwelingen (2007), Human Heredity64, 5,15) by adding a genotypic effect to the mean. The corresponding score test is a weighted family-based association tests statistic, where the weight depends on the linkage effect and on other genetic and shared environmental effects. For testing of genetic association in the presence of gene,covariate interaction, we propose a linear regression method where the family-specific score statistic is regressed on family-specific covariates. Both statistics are straightforward to compute. Simulation results show that adjusting the weight for the within-family variance structure may be a powerful approach in the presence of environmental effects. The test statistic for genetic association in the presence of gene,covariate interaction improved the power for detecting association. For illustration, we analyze the rheumatoid arthritis data from GAW15. Adjusting for smoking and anti-cyclic citrullinated peptide increased the significance of the association with the DR locus. [source]