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Stoke-on-Trent, United Kingdom

Haywood K.L.,University of Warwick | Packham J.C.,University of Birmingham | Packham J.C.,Haywood Rheumatology Center | Jordan K.P.,Keele University
Rheumatology (United Kingdom) | Year: 2014

Objective. The aim of this study was to explore the value of assessing fatigue frequency and its relationship with fatigue severity in a UK cohort of AS patients. Methods. Single items from the Evaluation of AS Quality of Life and BASDAI were used to measure fatigue frequency and severity, respectively. Items were included in a questionnaire containing AS-specific and generic measures, completed by participants in a postal survey at baseline and 6 months. Respondents were categorized at baseline into four groups according to fatigue frequency and severity and compared on other measures of health status. Results. Of baseline responders who experienced fatigue (n = 451, 74%), 75% reported it to be frequent and severe, 15% frequent not severe and 10% severe not frequent. There was no difference between groups on gender, age or years with AS. Patients reporting frequent and severe fatigue had worse scores than other groups across all other health status measures. Patients reporting only frequent fatigue had similar scores to those reporting only severe fatigue, but worse than those without fatigue. Eighty-one per cent of non-fatigued patients and 79% of those with frequent and severe fatigue at baseline did not change their level of fatigue at 6 months. However, 80% of patients with frequent or severe fatigue at baseline changed, mainly to no fatigue (43%) or both frequent and severe fatigue (30%). Conclusion. Routinely assessing both the frequency and severity of fatigue is important in understanding the impact of fatigue and its change over time. Not assessing frequency could result in the failure to identify patients with significant fatigue. However, the multidimensional nature of fatigue should be further explored. © The Author 2013. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.

Chen Y.,Haywood Rheumatology Center | Chen Y.,Keele University | Mattey D.L.,Haywood Rheumatology Center | Mattey D.L.,Keele University
Clinical and Experimental Rheumatology | Year: 2012

Objective: The present paper aims to investigate whether polymorphisms in the vascular endothelial growth factor A (VEGFA) gene and the loci of matrix metalloproteinase (MMP) 1 and 3 genes are associated with age at onset of RA. Methods: A sample of 413 hospital-based RA patients of Caucasian origin was studied. Common single-nucleotide polymorphisms (SNP) with likely importance were typed, including rs699947, rs833061, rs2010963 and rs3025039 in VEGFA, and rs1799750 in the MMP1 gene, rs3025058, rs679620 in the MMP3 gene and rs495366 located within the region between the MMP1 and MMP3 genes. Age at onset of RA was obtained on each patient. Demographic variables, smoking information, and a core set of clinical characteristics measured at recruitment were recorded. Hazard ratios (HR) that measured the effect size of genetic risk on age at RA onset were computed using Cox regression models. Results: The T allele at rs3025039 was associated with an increased risk of early onset (HR=1.25 [95% CI 1.0-1.58] for the risk over time; HR=1.84 [95% CI 1.20-2.83] for the risk of onset <40 years old). The AA genotype at rs495366 was also associated with an increased risk (HR=1.92 [95% CI 1.27-2.89] over time; HR=2.54 [95% CI 1.30-4.95] for onset <40 years old). These associations were independent of other risk factors such as sex, smoking and anti-CCP status. Conclusion: Polymorphisms in the VEGFA gene and the MMP1-3 intergenic locus may influence age at onset of RA. © CLINICAL AND EXPERIMENTAL RHEUMATOLOGY 2012.

Glossop J.R.,Keele University | Glossop J.R.,Haywood Rheumatology Center | Nixon N.B.,Haywood Rheumatology Center | Emes R.D.,University of Nottingham | And 7 more authors.
Epigenetics | Year: 2013

Multiple reports now describe changes to the DNa methylome in rheumatoid arthritis and in many cases have analyzed methylation in mixed cell populations from whole blood. however, these approaches may preclude the identification of cell type-specific methylation, which may subsequently bias identification of disease-specific changes. To address this possibility, we conducted genome-wide DNa methylation profiling using humanMethylation450 Beadchips to identify differences within matched pairs of T-lymphocytes and B-lymphocytes isolated from the peripheral blood of 10 healthy females. array data were processed and differential methylation identified using NIMBL software. Validation of array data was performed by bisulfite pyrosequencing. Genome-wide DNa methylation was initially determined by analysis of LINE-1 sequences and was higher in B-lymphocytes than matched T-lymphocytes (69.8% vs. 65.2%, P ≤ 0.01). Pairwise analysis identified 679 cpGs, representing 250 genes, which were differentially methylated between T-lympho-cytes and B-lymphocytes. The majority of sites (76.6%) were hypermethylated in B-lymphocytes. Pyrosequencing of selected candidates confirmed the array data in all cases. hierarchical clustering revealed perfect segregation of samples into two distinct clusters based on cell type. Differentially methylated genes showed enrichment for biological functions/pathways associated with leukocytes and T-lymphocytes. Our work for the first time shows that T-lymphocytes and B-lymphocytes possess intrinsic differences in DNa methylation within a restricted set of functionally related genes. These data provide a foundation for investigating DNa methylation in diseases in which these cell types play important and distinct roles. © 2013 Landes Bioscience.

Green D.J.,Keele University | Muller S.,Keele University | Mallen C.D.,Keele University | Hider S.L.,Keele University | Hider S.L.,Haywood Rheumatology Center
Scandinavian Journal of Rheumatology | Year: 2015

Objectives: Polymyalgia rheumatica (PMR) is the commonest inflammatory disorder of older adults. Although not part of the recently published classification criteria, patients with PMR frequently complain of fatigue. We compared consultation for fatigue and sleep problems between individuals with and without PMR. Method: Consulters receiving a Read-coded diagnosis of PMR at nine general practices between 2000 and 2009 were matched by age, gender, general practice, and year of consultation to four patients without PMR. Fatigue and sleep problems were defined using Read codes. Cox regression was used to determine the association between PMR diagnosis and consultation for a fatigue/sleep problem. Results: In total, 549 PMR patients were identified. Their mean (SD) age was 73.9 (8.6) years and 71% of the participants were female. Prior to the index date, 33 PMR patients and 80 matched non-PMR patients consulted with fatigue (0.43 vs. 0.25 consultations per 10 000 person-years, p = 0.006). PMR was associated with significantly more multiple fatigue consultations in the 12 months before PMR diagnosis [hazard ratio (HR) 1.95, 95% confidence interval (CI) 1.23-3.08]; no significant difference was seen in rates of consultations for sleep problems between patients with and without PMR. Conclusions: PMR patients were significantly more likely to have had multiple fatigue consultations before being diagnosed with PMR. Given the overproduction of inflammatory cytokines seen in PMR, this fatigue may represent a prodromal phase prior to consulting with more classical musculoskeletal symptoms. This suggests that clinicians should consider PMR as a potential diagnosis in older patients consulting with fatigue. © 2015 Taylor & Francis on license from Scandinavian Rheumatology Research Foundation.

Chen Y.,Haywood Rheumatology Center | Chen Y.,Keele University | Yu Z.,Keele University | Packham J.C.,Haywood Rheumatology Center | And 2 more authors.
PLoS ONE | Year: 2013

Objectives:To investigate whether normal variation of adult height is associated with clinical characteristics in rheumatoid arthritis (RA), including disease activity (DAS28), impairment of joint function (mechanical joint score, MJS) and overall disability (health assessment questionnaire, HAQ).Methods:A cohort (134 males, 287 females) of consecutively recruited RA patients of Northern European origin was studied. Height, weight and demographic information were obtained. A core set of disease measurements, including DAS28, MJS and HAQ, were recorded at baseline, 12 and 24 months. Other clinical variables (e.g. disease duration, IgM rheumatoid factor, antibodies to cyclic citrullinated peptide, C-reactive protein, erythrocyte sedimentation rate) were recorded at baseline. Socioeconomic status, smoking status, comorbid condition, other autoimmune conditions and drug therapy were also recorded. Associations were analyzed using univariate statistics and multivariate linear regression models. Mediation tests were also carried out for evaluating the relationship between gender, height and disease measures.Results:In males, height was inversely associated with DAS28, MJS and HAQ (at baseline and over 24 months) independent of other factors (e.g. weight, body mass index, age, disease duration, osteoporosis, autoantibodies, erosive disease, joint replacement, steroid use, smoking status, socioeconomic status and comorbid disease). In females, a similar trend was seen but the relationships were non significant. In the whole population, the association of female gender with more active disease and poor function disappeared after adjustment for height. Mediation analysis indicated that height served as a full mediator in the relationship of gender with disease activity and overall disability. Confirmation of these findings was demonstrated in a second RA population (n = 288).Conclusion:Adult height is inversely associated with disease activity, impairment of joint function and overall disability in RA, particularly in males. The association of female sex with more severe disease activity and disability appears to be mediated by smaller stature. © 2013 Chen et al.

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