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W Thomson

Publications and source records attributed to W Thomson.

187 records · Page 11Linked to original sources
PubMedDate not supplied

Influence of HLA-DRB1 and TNF microsatellite polymorphisms on the expression of extraarticular manifestations in rheumatoid arthritis patients from northwest Spain.

OBJECTIVE: To determine whether extraarticular manifestations (EAM) in rheumatoid arthritis (RA) patients from northwest (NW) Spain are associated with particular HLA-DRB1 alleles and/or TNF microsatellite polymorphisms. METHODS: The frequencies of HLA-DRB1 alleles and TNF microsatellite polymorphisms were compared between RA patients with and without extraarticular disease in a population from Lugo, NW Spain. HLA-DRB1 and TNF typing were carried out using molecular based methods on 181 clinic-based RA patients and 145 healthy controls. Associations were investigated using Chi-square analyses or Fisher's exact test. Multivariate logistic regression analyses were used to investigate independent and interactive effects of HLA and TNF alleles. RESULTS: The frequencies of HLA-DRB1 and TNF microsatellite polymorphisms in patients with EAM were not significantly different from those without extraarticular disease, although an association between HLA-DRB1*0101 and nodular disease approached significance (p = 0.054). There was no evidence for an increased frequency of homozygous or heterozygous combinations of disease associated DRB1 alleles in RA patients with EAM. The TNF a8 microsatellite allele was found at a higher frequency (6.9%) in patients with EAM compared to those without EAM (1.8%), and controls (1.5%) (p = 0.03 and 0.02, respectively). However significance was lost after correction for multiple testing. No evidence was foundfor an interaction between HLA-DRB1 and TNF alleles being associated with the expression of EAM. CONCLUSION: In an RA population from NW Spain the frequencies of HLA-DRB1 and TNF microsatellite alleles in patients with extra-articular manifestations were not significantly different to those without extraarticular disease, although there was a trend towards increased frequency of HLA-DRB1*0101 in patients with nodular disease. There was no evidence for an interaction between HLA-DRB1 and TNF alleles in relation to the expression of EAM.

Arthritis, Rheumatoid↗
PubMedDate not supplied

Corticotropin releasing hormone promoter polymorphisms in giant cell arteritis and polymyalgia rheumatica.

OBJECTIVE: Giant cell (temporal) arteritis (GCA) and polymyalgia rheumatica (PMR) are different but overlapping diseases of unknown etiology affecting the elderly. Corticotropin-releasing hormone (CRH) helps to regulate the immune response and maintain homeostasis during inflammatory stress. CRH promoter region polymorphisms in the 5'regulatory region of the CRH gene have been described. To investigate the possible implications of the CRH promoter polymorphisms in PMR and GCA susceptibility we have examined a series of patients with these conditions. METHODS: Sixty-two patients with biopsy-proven GCA, 86 patients with isolated PMR and 147 ethnically matched controls from the Lugo region of Northwest Spain were included in this study. Patients and controls were genotyped for CRH polymorphism in the 5' regulatory region of the gene at position 1273 (alleles A1 andA2) and at position 225 (alleles B1 and B2) by PCR-restriction fragment length polymorphism. Allele frequencies and genotype distribution were evaluated by the chi-square test. RESULTS: When GCA and PMR patients were examined for alleles and genotypes for each CRH polymorphism no significant differences in frequency were found compared with controls. A higher CRH-A2 allele frequency was observed in GCA patients with visual complications (21.4%) compared with controls (9.2%) and GCA cases without eye involvement [6.3%; p= 0.017, Pcorr = 0.034, O.R: 4.1 (95% CI 1.2- 13.9)], although this was based on a small sample of patients with ischemic visual complications (n = 14) and should be interpreted with caution. No differences in CRH allele or genotype frequencies were observed in isolated PMR patients stratified by relapses and recurrence of disease symptoms. CONCLUSION: Polymorphisms in the CRH gene regulatory region do not appear to be associated with increased susceptibility to PMR or GCA. The CRH-A2 allele may encode risk for the development of visual complications in GCA, although further studies to confirm this will be required.

Aged↗
PubMedDate not supplied

IL-6 promoter polymorphism at position -174 modulates the phenotypic expression of polymyalgia rheumatica in biopsy-proven giant cell arteritis.

OBJECTIVES: Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are related diseases in which diverse genetic and environmental factors are implicated. Both GCA and PMR are characterized by an intense acute phase reaction. In these sYndromes the increased production of IL-6 has been observed. To investigate further the genetic influence of IL-6 in GCA and PMR we have examined the IL-6 promoter polymorphism (G to C) at position -174 in the 5' region in a series of patients from Northwest Spain diagnosed with GCA and/or PMR. METHODS: Sixtxy-two biopsy-proven GCA patients (30 of them with associated PMR) and 84 patients with isolated PMR were studied. Patients and ethnically matched controls (n = 124) were from the Lugo region (Galicia, Northwest Spain). Patients and controls were genotyped for HLA-DRB1 and IL-6 polymorphism at position -174 by molecular methods. RESULTS: IL-6-174 allele C was marginally increased infrequency in GCA patients with PMR manifestations compared with isolated GCA (Pcorr 0.06; OR = 2.3). The increase in the frequency of the CC genotype in GCA patients with PMR versus those with isolated GCA was statistically significant (Pcorr 0.02). The increased frequency of allele C in GCA patients with PMR was more commonly observed in HLA-DRBI *04 negative patients. However, this polymorphism was not associated with a higher risk of ischemic events in GCA or with relapses in PMR. CONCLUSION: Allele C at position -174 in the 5' promoter region of the IL-6 gene may be associated with PMR in biopsy-proven GCA patients not carrying HLA-DRBI *04 alleles.

Alleles↗