Biomedical subjects

Emma Shelley

Publications and source records attributed to Emma Shelley.

3 recordsLinked to original sources

PubMed2002

Mutation screening of the macrophage migration inhibitory factor gene: positive association of a functional polymorphism of macrophage migration inhibitory factor with juvenile idiopathic arthritis.

OBJECTIVE: To determine if polymorphisms of the macrophage migration inhibitory factor (MIF) gene are associated with juvenile idiopathic arthritis (JIA). METHODS: Denaturing high-performance liquid chromatography was used to screen the MIF gene in 32 UK Caucasian controls and 88 UK Caucasian JIA patients. Ninety-two healthy UK Caucasian controls were then genotyped for each of the polymorphic positions identified. A panel of 526 UK Caucasian JIA patients and 259 UK Caucasian controls were subsequently genotyped for a single-nucleotide polymorphism (SNP) identified in the 5'-flanking region of the gene, using SNaPshot ddNTP primer extension and capillary electrophoresis. The functional significance of this polymorphism was also studied using luciferase-based reporter gene assays in human T lymphoblast and epithelial cell lines. RESULTS: A tetranucleotide repeat CATT((5-7)) beginning at nucleotide position -794 and 3 SNPs at positions -173 (G to C), +254 (T to C), and +656 (C to G) of the MIF gene were identified. No JIA-specific mutations were found. Allele and genotype frequencies differed significantly between the controls and the JIA patients for the MIF-173 polymorphism. Individuals possessing a MIF-173*C allele had an increased risk of JIA (34.8% versus 21.6%) (odds ratio 1.9, 95% confidence interval 1.4-2.7; P = 0.0002). Furthermore, the MIF-173* G and C variants resulted in altered expression of MIF in a cell type-specific manner. Serum levels of MIF were also significantly higher in individuals who carried a MIF-173*C allele (P = 0.04). CONCLUSION: The -173-MIF*C allele confers increased risk of susceptibility to JIA. Our data suggest a cell type-specific regulation of MIF, which may be central to understanding its role in inflammation.

Alleles↗

PubMed2002

Lack of association between juvenile idiopathic arthritis and fas gene polymorphism.

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a complex genetic disease of autoimmune etiology. Fas is a molecule with a pivotal role in apoptosis and hence in immune regulation. Elevated transcriptional levels of Fas in the synovial fluid of patients with JIA suggest that it might be implicated in disease etiopathogenesis. We investigated whether a polymorphism in the Fas promoter region (-670) confers susceptibility to JIA. METHODS: In this association study, 342 UK patients with JIA and 255 healthy individuals were genotyped for the polymorphism using polymerase chain reaction restriction fragment length polymorphism. Comparisons of the genotypic frequencies were made using chi-square analysis. RESULTS: No statistically significant differences were found when the genotype frequencies of the -670 Fas polymorphism were compared between the JIA cases and the control panel. Similarly, no differences were seen between the JIA subgroups, or when the patients were divided on the basis of rheumatoid factor or antinuclear antibody positivity. CONCLUSION: The -670 polymorphism of Fas does not appear to be associated with susceptibility to JIA.

Apoptosis↗

PubMed2002

Intercellular adhesion molecule-1 gene polymorphisms in isolated polymyalgia rheumatica.

OBJECTIVE: In untreated polymyalgia rheumatica (PMR), high levels of circulating soluble intercellular adhesion molecule-1 (ICAM-1) have been observed. To investigate the clinical implication of ICAM-1 polymorphisms in isolated PMR, we examined their potential influence in an unselected series of patients. METHODS: We studied 72 patients with isolated PMR and 129 ethnically matched controls from Lugo, Spain. Patients and controls were genotyped for HLA-DRB1 and ICAM-1 polymorphism at codons 241 and 469 by molecular methods. RESULTS: The distribution of alleles and genotypes for each ICAM-1 polymorphism did not show significant differences between patients with isolated PMR and controls. There were also no associations between ICAM-1 polymorphisms and relapses of the disease. The latter was primarily associated with carriage of an HLA-DRB1*0401 allele (OR 7.2, p = 0.01), although all relapsed patients with HLA-DRB1*0401 also carried the GG genotype of the ICAM-1 polymorphism at codon 241. The presence of both HLA-DRB1*0401 and the GG241 ICAM-1 genotype gave an OR of 15.2 (p = 0.005) after correction for age and sex. CONCLUSION: Although ICAM-1 polymorphisms alone do not appear to be associated with disease severity in isolated PMR, the presence of both HLA-DRB1*0401 and the ICAM-1 codon 241 GG homozygosity was significantly associated with increased risk of relapses in these patients.

Gene Frequency↗