38 research outputs found
Recommended from our members
Smoking is not linked to the development of anti-peptidylarginine deiminase 4 autoantibodies in rheumatoid arthritis
Background: Defining environmental factors responsible for development of autoimmunity in rheumatoid arthritis (RA) is critical for understanding mechanisms of disease initiation and propagation. Notably, a history of cigarette smoking has been implicated in the genesis of RA and is associated with worse disease outcomes. Antibodies to peptidylarginine deiminase 4 (PAD4) are also associated with more severe RA. A subset of patients who have PAD4 autoantibodies that cross-react with PAD3 (anti-PAD3/4) are at the highest risk for interstitial lung disease, and this risk is augmented by a history of cigarette smoking. It is unclear, however, if smoking is etiologically linked to the development of anti-PAD4 antibodies. Methods: Patients were included in this study if they had physician-diagnosed RA as well as DNA, serum, and a date-matched clinical assessment (n = 274). Anti-PAD4 and anti-CCP antibodies were measured by immunoprecipitation and ELISA, respectively; shared epitope (SE) status was determined by HLA-DRÎČ1 genotyping. Logistic regression analysis was used to evaluate associations of smoking with PAD4 antibodies, with adjustment for relevant demographic and clinical features. Stratified analyses by disease duration and shared epitope status were also performed. Results: Anti-PAD4 antibodies were present in 25% of RA patients, with 50% of these individuals having anti-PAD3/4 cross-reactive antibodies. Anti-PAD4 antibodies were significantly associated with a longer disease duration, SE alleles, and anti-CCP antibodies. Importantly, there were no significant differences in smoking history between anti-PAD4 positive and negative groups in univariate analyses, stratified analyses, or multivariable models. However, an inverse relationship between smoking and anti-PAD4 antibodies was suggested by a lower prevalence of current smokers among patients with anti-PAD3/4 antibodies compared to antibody negative individuals (p = 0.04). Further, the lowest levels of anti-PAD4 antibodies were observed in current smokers (p = 0.14), and a significant association of SE and anti-PAD4 antibodies was only present among never smokers (p = 0.01). Conclusions: Smoking history was not associated with anti-PAD4 antibodies in patients with RA. The finding that anti-PAD4 antibodies were not associated with smoking suggests that other environmental factors may contribute to the development of autoimmunity to PAD4 in these patients
Recommended from our members
Effects of Lowering Glycemic Index of Dietary Carbohydrate on Plasma Uric Acid: The OmniCarb Randomized Clinical Trial
OBJECTIVE:
The effects of carbohydrates on plasma uric acid levels are a subject of controversy. We determined the individual and combined effects of carbohydrate quality (the glycemic index) and quantity (the proportion of total daily energy [percentage of carbohydrates]) on uric acid levels.
METHODS:
We conducted a randomized, crossover trial of 4 different diets in overweight or obese adults without cardiovascular disease (nâ=â163). Participants consumed each of 4 diets over a 5-week period, each of which was separated by a 2-week washout period. Body weight was kept constant. The 4 diets were high glycemic index (â„65) with high percentage of carbohydrates (58% kcal), low glycemic index (â€45) with low percentage of carbohydrates (40% kcal), low glycemic index with high percentage of carbohydrates, and high glycemic index with low percentage of carbohydrates. Plasma uric acid levels were measured at baseline and after completion of each 5-week period for comparison between the 4 diets.
RESULTS:
Of the 163 study participants, 52% were women and 50% were non-Hispanic African American subjects; their mean age was 52.6 years, and their meanâ±âSD uric acid level was 4.7â±â1.2 mg/dl. Reducing the glycemic index lowered uric acid levels when the percentage of carbohydrates was low (-0.24 mg/dl; P < 0.001) or high (-0.17 mg/dl; P < 0.001). Reducing the percentage of carbohydrates marginally increased the uric acid level only when the glycemic index was high (Pâ=â0.05). The combined effect of lowering the glycemic index and increasing the percentage of carbohydrates was -0.27 mg/dl (P < 0.001). This effect was observed even after adjustment for concurrent changes in kidney function, insulin sensitivity, and products of glycolysis.
CONCLUSION:
Reducing the glycemic index lowers uric acid levels. Future studies should examine whether reducing the glycemic index can prevent gout onset or flares
2020 American College of Rheumatology Guideline for the Management of Gout
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155484/1/art41247.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155484/2/art41247_am.pd
Epigenome-wide association study of serum urate reveals insights into urate co-regulation and the SLC2A9 locus
Elevated serum urate levels, a complex trait and major risk factor for incident gout, are correlated with cardiometabolic traits via incompletely understood mechanisms. DNA methylation in whole blood captures genetic and environmental influences and is assessed in transethnic meta-analysis of epigenome-wide association studies (EWAS) of serum urate (discovery, nâ=â12,474, replication, nâ=â5522). The 100 replicated, epigenome-wide significant (pâ<â1.1Eâ7) CpGs explain 11.6% of the serum urate variance. At SLC2A9, the serum urate locus with the largest effect in genome-wide association studies (GWAS), five CpGs are associated with SLC2A9 gene expression. Four CpGs at SLC2A9 have significant causal effects on serum urate levels and/or gout, and two of these partly mediate the effects of urate-associated GWAS variants. In other genes, including SLC7A11 and PHGDH, 17 urate-associated CpGs are associated with conditions defining metabolic syndrome, suggesting that these CpGs may represent a blood DNA methylation signature of cardiometabolic risk factors. This study demonstrates that EWAS can provide new insights into GWAS loci and the correlation of serum urate with other complex traits
Epigenome-wide association study of serum urate reveals insights into urate co-regulation and the SLC2A9 locus
Serum urate concentration can be studied in large datasets to find genetic and epigenetic loci that may be related to cardiometabolic traits. Here the authors identify and replicate 100 urate-associated CpGs, which provide insights into urate GWAS loci and shared CpGs of urate and cardiometabolic traits.Elevated serum urate levels, a complex trait and major risk factor for incident gout, are correlated with cardiometabolic traits via incompletely understood mechanisms. DNA methylation in whole blood captures genetic and environmental influences and is assessed in transethnic meta-analysis of epigenome-wide association studies (EWAS) of serum urate (discovery, n = 12,474, replication, n = 5522). The 100 replicated, epigenome-wide significant (p < 1.1E-7) CpGs explain 11.6% of the serum urate variance. At SLC2A9, the serum urate locus with the largest effect in genome-wide association studies (GWAS), five CpGs are associated with SLC2A9 gene expression. Four CpGs at SLC2A9 have significant causal effects on serum urate levels and/or gout, and two of these partly mediate the effects of urate-associated GWAS variants. In other genes, including SLC7A11 and PHGDH, 17 urate-associated CpGs are associated with conditions defining metabolic syndrome, suggesting that these CpGs may represent a blood DNA methylation signature of cardiometabolic risk factors. This study demonstrates that EWAS can provide new insights into GWAS loci and the correlation of serum urate with other complex traits.</p