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.
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.
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.
The -670 polymorphism of Fas does not appear to be associated with susceptibility to JIA.
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.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Objective To compare the effects of a modified-fat diet high in monounsaturated fat, and a low-fat/high-carbohydrate diet on arterial elasticity.
Design Randomized crossover design; each diet period ...was 1 month and a 2-week wash out period occurred in between.
Subjects/setting Thirty healthy, free-living, nonsmoking men and women were recruited from the Melbourne, Australia, metropolitan region of Australia. Men were aged 35 to 55 years and postmenopausal women were aged 50 to 60 years and were not taking hormone replacement therapy. Twenty-eight subjects completed the study.
Intervention Two diets of equal energy value: a modified-fat diet and a low-fat/high-carbohydrate diet; the modified-fat diet had 3 times more energy from monounsaturated fat.
Main outcome measures Arterial elasticity and serum lipoprotein concentrations.
Statistical analysis The general linear model was used to investigate overall effect and any carryover or order effects. Paired
t test and the general linear model were used to compare the results from the 2 diet periods.
Results High-density lipoprotein cholesterol concentration was significantly higher on the modified-fat diet than on the low-fat/low-carbohydrate diet. Arterial elasticity and concentrations of total cholesterol, low-density lipoprotein cholesterol, and triglycerides were not significantly different on the 2 diets.
Applications/conclusions There is no evidence to favor a diet high in monounsaturated fat over a low-fat/high-carbohydrate diet because of an effect on arterial elasticity. Other changes in diet may be needed to cause a beneficial effect on arterial elasticity.
J Am Diet Assoc. 2000;100:537-542.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objective
To investigate SLC26A2, the gene that causes diastrophic dysplasia, in juvenile idiopathic arthritis (JIA).
Methods
Nine polymorphisms across the SLC26A2 gene locus were investigated using ...MassArray genotyping in 826 UK Caucasian JIA cases and 617 ethnically matched healthy controls.
Results
Significant associations between multiple single‐nucleotide polymorphisms (SNPs) across SLC26A2 and systemic‐onset JIA were found. In each case, homozygosity for the minor allele conferred the increased risk of disease susceptibility: rs1541915 (odds ratio OR 2.3, 95% confidence interval 95% CI 1.4–3.7, P = 0.0003), rs245056 (OR 2.8, 95% CI 1.7–4.6, P = 0.00002), rs245055 (OR 2.5, 95% CI 1.2–5.0, P = 0.004), rs245051 (OR 2.3, 95% CI 1.4–3.7, P = 0.0005), rs245076 (OR 2.7, 95% CI 1.3–5.4, P = 0.0015), and rs8073 (OR 2.3, 95% CI 0.9–5.6, P = 0.04).
Conclusion
These findings show the value of using monogenic disease loci as candidates for investigation in JIA. We identified a subgroup‐specific association between SNPs within the SLC26A2 gene and systemic‐onset JIA. Our findings also highlight systemic‐onset JIA as being a distinctly different disease from that in the other JIA subgroups.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
PDF
