Dataset Information

Genetic polymorphisms modifying oxidative stress are associated with disease activity in rheumatoid arthritis patients.

ABSTRACT: Reactive oxygen and nitrogen species are involved in the pathology of rheumatoid arthritis (RA). Polymorphisms in genes coding for superoxide dismutases (SOD2 and SOD3), catalase (CAT), tumor necrosis factor-alpha (TNFA) and inducible NO synthase (NOS2A) may influence RA activity. We determined SOD2 Ala-9Val, SOD3 Arg213Gly, CAT C-262T, TNFA G-308A, TNFA C-857T and NOS2A (CCTTT) (n)polymorphisms in 327 RA patients. Carriers of CAT -262T and TNFA -308A allele had lower mean disease activity score of 28 joint count (DAS28) values than patients with CAT -262CC and TNFA -308GG genotypes (p = 0.014 and p = 0.046, respectively). Patients with the combination of CAT -262T and TNFA -308A allele had lower mean DAS28 values and a higher probability for low disease activity than non-carriers (p = 0.003, OR = 3.585, 95% CI = 1.538-8.357). Our results suggest that CAT and TNFA polymorphisms alone and in combination influence the activity of RA.

SUBMITTER: Bohanec Grabar P

PROVIDER: S-EPMC3833245 | biostudies-other | 2009

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Genetic polymorphisms modifying oxidative stress are associated with disease activity in rheumatoid arthritis patients.

Bohanec Grabar Petra P Logar Dussan D Tomsic Matija M Rozman Blaz B Dolzan Vita V

Disease markers 20090101 1

Reactive oxygen and nitrogen species are involved in the pathology of rheumatoid arthritis (RA). Polymorphisms in genes coding for superoxide dismutases (SOD2 and SOD3), catalase (CAT), tumor necrosis factor-alpha (TNFA) and inducible NO synthase (NOS2A) may influence RA activity. We determined SOD2 Ala-9Val, SOD3 Arg213Gly, CAT C-262T, TNFA G-308A, TNFA C-857T and NOS2A (CCTTT) (n)polymorphisms in 327 RA patients. Carriers of CAT -262T and TNFA -308A allele had lower mean disease activity score ...[more]

PMID: 19242068

Similar Datasets

Project description:BackgroundRheumatoid arthritis (RA) and Alzheimer's disease (AD) are inversely associated. To test the hypothesis that genetic elements associated with increased RA risk are associated with decreased AD risk, we evaluated RA genetic risk factors recently identified in genome-wide association studies (GWAS) for their association with AD in a two-stage, case-control analysis.ResultsIn our Stage 1 analysis of ~800 AD and ~1,200 non-AD individuals, three of seventeen RA-associated SNPs were nominally associated with AD (p < 0.05) with one SNP, rs2837960, retaining significance after correction for multiple testing (p = 0.03). The rs2837960_G (minor) allele, which is associated with increased RA risk, was associated with increased AD risk. Analysis of these three SNPs in a Stage 2 population, consisting of ~1,100 AD and ~2,600 non-AD individuals, did not confirm their association with AD. Analysis of Stage 1 and 2 combined suggested that rs2837960 shows a trend for association with AD. When the Stage 2 population was age-matched for the Stage 1 population, rs2837960 exhibited a non-significant trend with AD. Combined analysis of Stage 1 and the age-matched Stage 2 subset showed a significant association of rs2837960 with AD (p = 0.002, OR 1.24) that retained significance following correction for age, sex and APOE (p = 0.02, OR = 1.20). Rs2837960 is near BACE2, which encodes an aspartic protease capable of processing the AD-associated amyloid precursor protein. Testing for an association between rs2837960 and the expression of BACE2 isoforms in human brain, we observed a trend between rs2837960 and the total expression of BACE2 and the expression of a BACE2 transcript lacking exon 7 (p = 0.07 and 0.10, respectively).ConclusionsRA-associated SNPs are generally not associated with AD. Moreover, rs2837960_G is associated with increased risk of both RA and, in individuals less than 80 years of age, with AD. Overall, these results contest the hypothesis that genetic variants associated with RA confer protection against AD. Further investigation of rs2837960 is necessary to elucidate the mechanism by which rs2837960 contributes to both AD and RA risk, likely via modulation of BACE2 expression.

Project description:ObjectiveTo evaluate rheumatoid arthritis (RA) disease activity and risk of RA-associated interstitial lung disease (RA-ILD).MethodsWe investigated disease activity and risk of RA-ILD using the Brigham RA Sequential Study (BRASS, 2003-2016). All patients were diagnosed as having RA according to accepted criteria. Disease Activity Scores in 28 joints (DAS28) and covariate data were measured prospectively at annual study visits. Diagnosis of RA-ILD was determined by review of images from clinically indicated chest computed tomography scans. We analyzed patients without RA-ILD at baseline. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for RA-ILD, using annually updated DAS28 data, with adjustment for known RA-ILD risk factors (age, sex, smoking status, RA duration, and serologic status). We performed alternative analyses that did not censor at the time of missing DAS28 data and included adjustment for use of methotrexate, use of glucocorticoids, presence of bone erosions, and presence of rheumatoid nodules.ResultsAmong 1,419 participants, the mean ± SD age was 55.8 ± 14.2 years, and 68.6% were seropositive for either cyclic citrullinated peptide or rheumatoid factor. We identified 85 incident cases of RA-ILD during a mean ± SD follow-up duration of 8.9 ± 4.2 years per patient. The moderate/high disease activity group had a multivariable HR of 2.22 (95% CI 1.28-3.82) for RA-ILD compared to the remission/low disease activity group. Risk of RA-ILD increased across disease activity categories: multivariable HR 1.00 (reference) for remission, 1.41 (95% CI 0.61-3.28) for low disease activity, 2.08 (95% CI 1.06-4.05) for moderate disease activity, and 3.48 (95% CI 1.64-7.38) for high disease activity (P for trend = 0.001). For each unit increase in the DAS28, the risk of RA-ILD increased by 35% (95% CI 14-60%). Results were similar in analyses that included follow-up for missing DAS28 data and with adjustment for use of methotrexate, use of glucocorticoids, presence of bone erosions, or presence of rheumatoid nodules.ConclusionActive articular RA was associated with an increased risk of developing RA-ILD. These results suggest that decreasing systemic inflammation may alter the natural history of RA-ILD development.

Project description:BackgroundThe prevalence and pathophysiological mechanisms of cognitive deficits (CD) Systemic Lupus Erythematosus (SLE) and Rheumatoid arthritis (RA) are very heterogeneous and poorly understood. We characterized CD in patients with SLE compared with RA patients and healthy controls. We compared the neuropsychological profile of SLE and RA with patients' oxidative/inflammatory biomarkers for CD.MethodsWe performed a cross-sectional study, including 50 SLE patients, 29 RA patients, and 32 healthy controls. SLEDAI and DAS28 assessed disease activity. SF-36 questionnaire and a battery of cognitive tests were applied to all participants. Blood samples were collected to determine IL-6, S100ß, myeloperoxidase (MPO), malondialdehyde and reduced glutathione (GSH) alterations.ResultsIn the SLE group, higher GSH was associated with the absence of CD (With CD = 69 ± 49, Without CD = 112 ± 81, p = 0.030), while higher IL-6 was associated with the presence of CD in the RA group (With CD = 603 ± 173, Without CD = 431 ± 162, p = 0.032). Regarding specific cognitive domains, in SLE higher MPO was associated with poor performance in reasoning and abstraction (p = 0.039), higher IL-6 was associated with poor performance in inhibitory control and attention (p = 0.031), and higher GSH was associated with better performance in memory(p = 0.021). Higher SLEDAI was associated with poor performance in semantic fluency(p = 0.031), inhibitory control, and attention in the SLE group(p = 0.037). In the RA group, higher DAS-28 was associated with poor performance in executive functions(p = 0.016) and phonemic fluency (p = 0.003).ConclusionSLE patients' disease activity, inflammatory state, and oxidative stress were associated with CD. In RA patients, CD was associated with disease activity and inflammatory state. These results encourage further studies with larger samples aiming to confirm oxidative stress parameters as biomarkers of CD in SLE patients.

Dataset Information

Genetic polymorphisms modifying oxidative stress are associated with disease activity in rheumatoid arthritis patients.

Publications

Genetic polymorphisms modifying oxidative stress are associated with disease activity in rheumatoid arthritis patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets