Lower Risk Of Rheumatoid Arthritis Research Articles

Association of Diet Quality With Risk of Incident Rheumatoid Arthritis in the Women’s Health Initiative

BackgroundVarious foods and nutrients are linked with higher or lower risk of rheumatoid arthritis (RA), yet these associations are inconsistent across studies. Limited research has been done evaluating the association between diet quality and RA in a larger-scale prospective study on postmenopausal women. ObjectiveThe objective of this study was to evaluate the association between dietary quality and risk of incident RA in postmenopausal women. DesignThis was a prospective cohort study as part of the Women’s Health Initiative (WHI), with an average follow-up time of 8.1 years. Baseline diet was measured using a food frequency questionnaire (FFQ). Diet quality was evaluated by the Healthy Eating Index (HEI)-2015 total score. In addition, intake of food groups and nutrients that align with HEI-2015 components was assessed. Participants/settingPostmenopausal women (N = 109 591) were included in this study, which was conducted at various clinical centers across the United States with recruitment from 1993 to 1998. Women’s Health Initiative participants who were missing outcome data, had unreliable/missing FFQ data, or had RA at baseline were excluded. Main outcome measuresThe primary outcome measure was incident RA. Statistical analyses performed Multivariable Cox proportional regression analysis was performed evaluating the association of diet quality with self-reported physician-diagnosed RA after adjusting for age, race, ethnicity, education status, income, and body mass index (BMI). ResultsDuring 857 517 person-years of follow-up, 5823 incident RA cases were identified. After adjustment for multiple comparisons, compared with quartile 1, quartiles 2, 3, and 4 of the HEI-2015 total scores were associated with lower RA risks of 1%, 10%, and 19%, respectively (P-trend < .001). Greater consumption of total fruits (P-trend = .014), whole fruits (P-trend < .0002), total vegetables (P-trend = .008), greens and beans (P-trend < .0002), whole grains (P-trend = .008), and dairy (P-trend = .018) were significantly associated with lower rates of incident RA. Conversely, higher consumption of saturated fat (P-trend = .002) was significantly associated with higher rates of incident RA. ConclusionA higher-quality diet reflected by higher HEI-2015 total scores was inversely associated with incident RA in postmenopausal women.

Association between Life's Essential 8 and rheumatoid arthritis.

Rheumatoid arthritis (RA) exhibits a robust association with cardiovascular disease. Our study aims to elucidate the correlation between RA prevalence and Life's Essential 8 (LE8), a recently updated measure of cardiovascular health (CVH). We conducted a population-based cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) spanning from 2007 to 2018. Utilizing multivariable logistic and restricted cubic spline models, we explored the relationship between LE8 and RA. Our analysis included 17,263 participants. We found that higher LE8 scores were closely associated with reduced odds of RA (odds ratio for each 10-point increase, 0.91 (95% CI, 0.75-0.87)). Furthermore, we observed a nonlinear association between LE8 and RA after adjusting for potential confounders. Specifically, higher scores for sleep health, nicotine exposure, body mass index, and blood pressure within the LE8 components were significantly correlated with a lower risk of RA. Additionally, the inverse relationship between LE8 scores and RA was notably stronger among young and female individuals. Our findings suggest a negative correlation between LE8 and RA prevalence, indicating that adherence to the lifestyle defined by LE8 may confer protective effects against RA.

Identification of lipid-modifying drug targets for autoimmune diseases: insights from drug target mendelian randomization

BackgroundsA growing body of evidence has highlighted the interactions of lipids metabolism and immune regulation. Nevertheless, there is still a lack of evidence regarding the causality between lipids and autoimmune diseases (ADs), as well as their possibility as drug targets for ADs.ObjectivesThis study was conducted to comprehensively understand the casual associations between lipid traits and ADs, and evaluate the therapeutic possibility of lipid-lowering drug targets on ADs.MethodsGenetic variants for lipid traits and variants encoding targets of various lipid-lowering drugs were derived from Global Lipid Genetics Consortium (GLGC) and verified in Drug Bank. Summary data of ADs were obtained from MRC Integrative Epidemiology Unit (MER-IEU) database and FinnGen consortium, respectively. The causal inferences between lipid traits/genetic agents of lipid-lowering targets and ADs were evaluated by Mendelian randomization (MR), summary data-based MR (SMR), and multivariable MR (MVMR) analyses. Enrichment analysis and protein interaction network were employed to reveal the functional characteristics and biological relevance of potential therapeutic lipid-lowering targets.ResultsThere was no evidence of causal effects regarding 5 lipid traits and 9 lipid-lowering drug targets on ADs. Genetically proxied 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) inhibition was associated with a reduced risk of rheumatoid arthritis (RA) in both discovery (OR [odds ratio] = 0.45, 95%CI: 0.32, 0.63, P = 6.79 × 10− 06) and replicate datasets (OR = 0.37, 95%CI: 0.23, 0.61, P = 7.81 × 10− 05). SMR analyses supported that genetically proxied HMGCR inhibition had causal effects on RA in whole blood (OR = 0.48, 95%CI: 0.29, 0.82, P = 6.86 × 10− 03) and skeletal muscle sites (OR = 0.75, 95%CI: 0.56, 0.99, P = 4.48 × 10− 02). After controlling for blood pressure, body mass index (BMI), smoking and drinking alchohol, HMGCR suppression showed a direct causal effect on a lower risk of RA (OR = 0.33, 95%CI: 0.40, 0.96, P = 0.042).ConclusionsOur study reveals causal links of genetically proxied HMGCR inhibition (lipid-lowering drug targets) and HMGCR expression inhibition with a decreased risk of RA, suggesting that HMGCR may serve as candidate drug targets for the treatment and prevention of RA.

Association of HMGCR inhibition with rheumatoid arthritis: a Mendelian randomization and colocalization study.

The objective of this study was to investigate the association between hydroxymethylglutaryl coenzyme A reductase (HMGCR) inhibition and rheumatoid arthritis (RA) using drug-target Mendelian randomization (MR) and genetic colocalization analyses. Two sets of genetic instruments were employed to proxy HMGCR inhibitors: expression quantitative trait loci (eQTLs) of target genes from the eQTLGen Consortium and genetic variants associated with low-density lipoprotein cholesterol (LDL-C) levels with HMGCR locus from open genome-wide association studies (GWAS). Positive control analyses were conducted on type 2 diabetes and coronary heart disease, and multiple sensitivity analyses were performed. Genetically proxied expression of eQTL was associated with a lower risk of RA (OR=0.996, 95% CI =0.992-0.999, p= 0.032). Similarly, hydroxymethylglutaryl coenzyme A reductase (HMGCR)-mediated low-density lipoprotein cholesterol was negatively associated with risk of RA (OR=0.995, 95% CI =0.991-0.998, p= 0.007) in the inverse variance weighted (IVW) method. Colocalization analysis suggested a 74.6% posterior probability of sharing a causal variant within the SNPs locus (PH4 = 74.6%). A causal relationship also existed between HMGCR-mediated LDL and RA risk factors. The results were also confirmed by multiple sensitivity analyses. The results in positive control were consistent with the previous study. Our study suggested that HMGCR inhibition was associated with an increased risk of RA while also highlighting an increased risk of current smoking and obesity. These findings contribute to a growing body of evidence regarding the adverse effects of HMGCR inhibition on RA risk, calling for further research on alternative approaches using HMGCR inhibitors in RA management.

Metabolic Signature of Healthy Lifestyle and Risk of Rheumatoid Arthritis: Observational and Mendelian Randomization Study

BackgroundAlthough substantial evidence reveals that healthy lifestyle behaviors are associated with a lower risk of rheumatoid arthritis (RA), the underlying metabolic mechanisms remain unclear. ObjectivesThis study aimed to identify the metabolic signature reflecting a healthy lifestyle and investigate its observational and genetic linkage with RA risk. MethodsThis study included 87,258 UK Biobank participants (557 cases with incident RA) aged 37–73 y with complete lifestyle, genotyping, and nuclear magnetic resonance (NMR) metabolomics data. A healthy lifestyle was assessed based on 5 factors: healthy diet, regular exercise, not smoking, moderate alcohol consumption, and normal body mass index. The metabolic signature was developed by summing the selected metabolites’ concentrations weighted by the coefficients using elastic net regression. We used the multivariate Cox model to assess the associations between metabolic signatures and RA risk, and examined the mediating role of the metabolic signature in the impact of a healthy lifestyle on RA. We performed genome-wide association analysis (GWAS) to obtain genetic variants associated with the metabolic signature and then conducted Mendelian randomization (MR) analyses to detect causality. ResultsThe metabolic signature comprised 81 metabolites, robustly correlated with a healthy lifestyle (r = 0.45, P = 4.2 × 10−15). The metabolic signature was inversely associated with RA risk (HR per standard deviation (SD) increment: 0.76; 95% CI: 0.70–0.83), and largely explained the protective effects of healthy lifestyle on RA with 64% (95% CI: 50.4–83.3) mediation proportion. 1- and 2-sample MR analyses also consistently showed the associations of genetically inferred per SD increment in metabolic signature with a reduction in RA risk (HR: 0.84; 95% CI: 0.75–0.94; and P = 0.002 and OR: 0.84; 95% CI: 0.73–0.97; and P = 0.02, respectively). ConclusionsOur findings implicate that the metabolic signature reflecting healthy lifestyle is a potential causal mediator in the development of RA, highlighting the importance of early lifestyle intervention and metabolic status tracking for precise prevention of RA.

Repurposing antidiabetic drugs for rheumatoid arthritis: results from a two-sample Mendelian randomization study

Despite increasing therapeutic options to treat rheumatoid arthritis (RA), many patients fail to reach treatment targets. The use of antidiabetic drugs like thiazolidinediones has been associated with lower RA risk. We aimed to explore the repurposing potential of antidiabetic drugs in RA prevention by assessing associations between genetic variation in antidiabetic drug target genes and RA using Mendelian randomization (MR). A two-sample MR design was used to estimate the association between the antidiabetic drug and RA risk using summary statistics from genome-wide association studies (GWAS). We selected independent genetic variants from the gene(s) that encode the target protein(s) of the investigated antidiabetic drug as instruments. We extracted the associations of instruments with blood glucose concentration and RA from the UK Biobank and a GWAS meta-analysis of clinically diagnosed RA, respectively. The effect of genetic variation in the drug target(s) on RA risk was estimated by the Wald ratio test or inverse-variance weighted method. Insulin and its analogues, thiazolidinediones, and sulfonylureas had valid genetic instruments (n = 1, 1, and 2, respectively). Genetic variation in thiazolidinedione target (gene: PPARG) was inversely associated with RA risk (odds ratio [OR] 0.38 per 0.1mmol/L glucose lowering, 95% confidence interval [CI] 0.20–0.73). Corresponding ORs (95%CIs) were 0.83 (0.44–1.55) for genetic variation in the targets of insulin and its analogues (gene: INSR), and 1.12 (0.83, 1.49) 1.25 (0.78-2.00) for genetic variation in the sulfonylurea targets (gene: ABCC8 and KCNJ11). In conclusion, genetic variation in the thiazolidinedione target is associated with a lower RA risk. The underlying mechanisms warrant further exploration.

Assessment of Bidirectional Relationships between Mental Illness and Rheumatoid Arthritis: A Two-Sample Mendelian Randomization Study.

A correlation between mental illness and systemic rheumatoid arthritis (RA) has been observed in several prior investigations. However, little is known about the causative relationship between them. The present study aimed to systematically investigate the potential association between genetically determined mental illness and RA. Two-sample bidirectional Mendelian randomization (MR) analysis was performed using publicly released genome-wide association studies (GWAS). We selected independent genetic variants associated with four mental illnesses (bipolar disorder, broad depression, major depression, and anxiety) as instrumental variables. The inverse variance weighted (IVW) method was used as the primary analysis to assess the causal relationship between mental illness and RA. Results of the IVW analysis suggested that genetic predisposition to bipolar disorder was associated with a decreased risk of RA (odds ratio [OR] = 0.825, 95% CI = 0.716 to 0.95, p = 0.007). Furthermore, we did not find a significant causal effect of RA on bipolar disorder in the reverse MR analysis (p > 0.05). In addition, our study found no evidence of a bidirectional causal relationship between genetically predicted broad depression, major depression, anxiety, and RA (p > 0.05). The genetically proxied bipolar disorder population has a lower RA risk, which may indicate that there is a hidden mechanism for inhibiting the pathogenesis of RA in bipolar disorder. However, results do not support a causal connection between depression, anxiety, and RA.

Association between 19 dietary fatty acids intake and rheumatoid arthritis: Results of a nationwide survey

BackgroundThe relationship between dietary fatty acid intakes and rheumatoid arthritis (RA) is unclear and the available studies have focused on only a few fatty acids. This study investigated the association between the intake of 19 dietary fatty acids and RA in U.S. adults. MethodsThis cross-sectional study using nationally representative data from the 2010-2020 National Health and Nutrition Examination Survey (NHANES). Multivariate linear regression model, multivariate logic regression models, smoothing curve fitting, and two-segment linear regression model were used to explore the relationships between 19 dietary fatty acids intakes with high-sensitivity C-reactive protein (Hs-CRP) and RA risk. ResultsA total of 16,530 participants were included (1053 participants with RA). Intake of hexadecanoic acid and octadecanoic acid were significantly associated with higher Hs-CRP levels, intake of hexadecenoic acid was significantly associated with higher RA risk, and intake of docosahexaenoic acid was significantly associated with lower RA risk. In addition, there was an inverted U-shaped relationship between total monounsaturated fatty acids (MUFAs) intake and RA risk, with the inflection point reached at 15.77% . ConclusionsAmong the 19 dietary fatty acids, only 4 subclasses were significantly associated with Hs-CRP or RA risk. The inverted U-shaped relationship between MUFAs and RA risk may provide insights to find potential prevention strategies for RA.

A Mendelian randomization study on causal effects of leisure sedentary behaviour on the risk of rheumatoid arthritis.

The causal inference between leisure sedentary behaviour (LSB) and rheumatoid arthritis (RA) is still controversial because of potential residual confounding and reverse causality. The present study used publicly available large-scale genome-wide association studies (GWAS) of LSB (television watching, computer use, and driving) and RA to perform a two-sample Mendelian randomization (MR) study to evaluate the causal effect of LSB on the risk of RA. We detected significant causal associations using the multiplicative random effects-inverse variance weighted (MRE-IVW) method, the maximum likelihood, robust adjusted profile scores, the weighted median, MR-Egger regression, and several complementary sensitivity analyses. Risk factor analysis was also conducted to further investigate potential mediators linking causal inference. Increased genetic liability to leisure television watching was significantly associated with a higher risk of RA (MRE-IVW method; OR=2.46, 95% CI 1.77-3.41; p=8.35 × 10-8 ). MR estimates indicated that prolonged leisure computer use was causally associated with a lower risk of RA (MRE-IVW method; OR=0.23, 95% CI 0.12-0.46; p=2.19 × 10-5 ). However, we found no evidence for a causal effect of leisure driving on the risk of RA (MRE-IVW method; OR=0.59, 95% CI 0.10-3.41; p=0.557). No pleiotropy was detected by the sensitivity analysis. This study supports a causal association between prolonged leisure television watching and an increased risk of RA. Additionally, prolonged computer use might be a protective factor for RA.

Association of Healthy Lifestyle Behaviors and the Risk of Developing Rheumatoid Arthritis Among Women.

To investigate whether a healthy lifestyle, defined by a healthy lifestyle index score (HLIS), was associated with rheumatoid arthritis (RA) risk, overall and with seropositive/seronegative subtypes. We analyzed female nurses in the Nurses' Health Study (NHS, 1986-2016) and NHSII (1991-2017). Lifestyle and medical information were collected on biennial questionnaires. Medical records confirmed incident RA and serostatus. The HLIS index includes 5 modifiable components: smoking, alcohol consumption, body mass index, physical activity, and diet. Cox regression, adjusted for confounders, modeled associations between HLIS and incident RA. The population attributable risk estimated the proportion of incident RA preventable if participants adopted ≥4 healthy lifestyle factors. A total of 1,219 incident RA cases (776 seropositive, 443 seronegative) developed in 4,467,751 person-years. Higher (healthier) HLIS was associated with lower overall RA risk (hazard ratio [HR] 0.86 [95% confidence interval (95% CI) 0.82-0.90]), seropositive RA risk (HR 0.85 [95% CI 0.80-0.91]), and seronegative RA risk (HR 0.87 [95% 0.80-0.94]). Women with 5 healthy lifestyle factors had the lowest risk (HR 0.42 [95% CI 0.22-0.80]). The population attributable risk for adhering to ≥4 lifestyle factors was 34% for RA. In this prospective cohort, healthier lifestyle was associated with a lower RA risk. A substantial proportion of RA may be preventable by a healthy lifestyle.

Adding Chinese Herbal Medicine to Routine Care is Associated With a Lower Risk of Rheumatoid Arthritis Among Patients With Asthma: A Population-Based Retrospective Cohort Study.

Objective: Due to the shared pathogenesis of asthma and rheumatoid arthritis (RA), patients with asthma were found to have a higher risk of RA. While the benefits and safety of Chinese herbal medicine (CHM) for asthma have been reported, the scientific evidence regarding its effect on RA is limited. This longitudinal cohort study aimed to determine the relation between CHM use and RA risk in patients with asthma. Methods: Using the nationwide claims data, we enrolled 33,963 patients 20–80 years of age who were newly diagnosed with asthma and simultaneously free of RA between 2000 and 2007. From this sample, we utilized propensity score matching to create sets of participants as treatment and control groups, which comprised 13,440 CHM users and 13,440 non-CHM users. The incidence rate and hazard ratio (HR) for RA between the two groups were estimated at the end of 2013. A Cox proportional hazards model was constructed to examine the impact of the CHM use on the risk of RA. Results: The cumulative incidence of RA was substantially lower in the CHM user group. In the follow-up period, 214 patients in the CHM user group (1.92 per 1,000 person-years) and 359 patients in the non-CHM user group (2.92 per 1,000 person-years) developed RA (adjusted HR = 0.63, 95% confidence interval: 0.54–0.75). Of the commonly-prescribed formulae, nine CHM products were associated with a lower RA risk: Xiao-Qing-Long-Tang, Ma-Xing-Gan-Shi-Tang, Ding-Chuan-Tang, Xin-Yi-Qing-Fei-Tang, Bei Mu, Jie Geng, Xing Ren, Da Huang, and San Chi. Conclusion: This study found that patients with asthma who received CHM treatment, in addition to the conventional therapy, had a lower risk of RA. Use of CHM treatment may be integrated into conventional therapy to reduce subsequent RA risk among asthma patients.

Sulfonylureas or biguanides is associated with a lower risk of rheumatoid arthritis in patients with diabetes: A nationwide cohort study.

ObjectiveDiabetes mellitus (DM) is associated with immune dysregulation, while sulfonylureas or biguanides have been linked to anti-inflammatory mechanisms. In this study, we aimed to examine the occurrence rate of rheumatoid arthritis (RA) among DM patients and its incidence rate between different treatments.MethodsThis cohort study used the Taiwan National Health Insurance Research Database between 1997 and 2013 to evaluate the primary outcomes of the preventive role of sulfonylureas or biguanides in the development of RA. We used the Chi-square test for categorical variables and Cox proportional hazard regression and log-rank test to explore the time for development of RA in DM patients. Logistic regression was adopted to estimate the odds ratio of RA in different dosages of medication exposure.ResultsOur cohort study included 94,141 DM cases. The risk of RA development of non-sulfonylureas/biguanides users among the DM group in each analysis was set as the reference, and the adjusted hazard ratio of RA in DM patients who were using sulfonylureas or biguanides was 0.73 (95% confidence interval 0.60–0.90). Within 1 year before the index date, compared with no-biguanides users, patients with more than 180 days of prescription of biguanides had a significantly lower RA risk. Similarly, the significantly lower risk of RA was still observed in DM patients who had more than 365 days of prescription of sulfonylurea within 2 or 3 years before the index date of first RA visit (all p < 0.05).ConclusionOur data suggest that sulfonylureas or biguanides are associated with a lower rate of RA development in patients with DM; the effect of biguanides appeared more rapid than that of sulfonylureas, but the sulfonylureas might have a longer effect on lowering RA development incidence.

Genetically Determined Circulating Levels of Cytokines and the Risk of Rheumatoid Arthritis.

Background: Accumulation of inflammatory leukocytes in articular tissues is the hallmark feature of rheumatoid arthritis (RA). Increasing evidence from observational studies has suggested that several cytokines may be involved in the development of RA. However, traditional observational studies are susceptible to bias from confounding and reverse causation; therefore, the potential causal relationships of individual cytokines with the risk of RA remain elusive. Objective: In this study, we evaluated whether genetically determined circulating levels of cytokines were associated with the risk of RA by performing Mendelian randomization (MR). Methods: We identified single nucleotide polymorphisms (SNPs) associated with circulating levels of cytokines and growth factors from a genome-wide association study (GWAS) including 8,293 participants of Finnish ancestry as instrumental variables (IVs). The association estimates of these IVs with the risk of RA were obtained from a GWAS meta-analysis including 14,361 RA cases and 43,923 controls of European ancestry. We conducted a series of MR analyses to assess the relationship between genetically determined circulating cytokines and the risk of RA, including the random-effects inverse variance-weighted, weighted-median, MR-Egger regression, and MR pleiotropy residual sum and outlier tests. For potential cytokine-RA associations supported by MR evidence, sensitivity analyses were further performed using restricted IV sets of SNPs with colocalization evidence and that excluding pleiotropic SNPs. Results: In the primary MR analysis, there was a suggestive inverse association between genetically determined circulating level of macrophage inflammatory protein-1β (MIP-1b) and the risk of RA [odds ratio (OR): 0.95, 95% confidence interval (CI) = 0.92-0.99, p = 0.016]. The effect estimates were similar in alternative MR analyses. Among SNPs used as IVs for MIP-1b, we found 92 SNPs without documented pleiotropy and three SNPs with evidence of colocalization. The association of MIP-1b with RA from sensitivity analyses using these two sets of restricted IVs remained stable. Conclusion: Our study suggests that genetically determined elevated circulating level of MIP-1b may be associated with a lower risk of RA. Further studies are warranted to determine how MIP-1b and related pathways may contribute to the development of RA.

Evaluating associations of joint swelling, joint stiffness and joint pain with physical activity in first-degree relatives of patients with rheumatoid arthritis: Studies of the Aetiology of Rheumatoid Arthritis (SERA), a prospective cohort study

ObjectivePhysical activity (PA) in preclinical rheumatoid arthritis (RA) is associated with lower RA risk and disease severity. As joint signs and symptoms of inflammatory arthritis serve as a barrier to...

Adherence to the dietary approaches to stop hypertension dietary pattern and rheumatoid arthritis in Iranian adults.

To examine the hypothesis that rheumatoid arthritis (RA) patients are less likely than healthy individuals to adhere to the dietary approaches to stop hypertension (DASH) dietary pattern. A multi-centre cross-sectional study involving a total of 300 eligible Iranian adults (aged >19 years; 93·0 % female) recruited during 2019-2020. Participants' actual dietary intakes were measured via self-administered 3-d dietary records. The DASH score was computed based on the energy-adjusted intakes of eight major dietary components usually emphasised (i.e. fruits, vegetables, nuts and legumes, low-fat dairy products and whole grains) or minimised (i.e. sweets, red or processed meats and sodium) in the DASH diet. The higher the DASH score of subjects, the greater their adherence to the DASH pattern. The outpatient clinics of major general hospitals in Shiraz, Iran. 100 incident cases with definite RA according to the 2010 American College of Rheumatology/European League Against Rheumatism Classification Criteria for RA and 200 apparently healthy controls frequency-matched by gender and age. After adjusting for several potential covariates in the binary logistic regression analysis, RA cases were less likely than controls to have high adherence to the DASH pattern (OR = 0·08; 95 % CI 0·03, 0·20; P = 0·001). Our findings in a sample of Iranian adults revealed that RA patients are less likely than healthy individuals to adhere to the DASH dietary pattern. However, the potential causal association of greater adherence to the DASH pattern and lower risk of RA needs to be confirmed by prospective studies of high methodological quality.

Causal association of monounsaturated fatty acids with rheumatoid arthritis but not osteoarthritis: A two-sample Mendelian randomization study

ObjectivesPrevious studies have indicated that dietary monounsaturated fatty acids (MUFAs) are associated with decreased risk of osteoarthritis (OA) and rheumatoid arthritis (RA). However, the causality of the observed associations is largely undetermined. We sought to ascertain the potential causal roles of two of the most common MUFAs, oleic acid and palmitoleic acid, in RA and OA risk using a two-sample Mendelian randomization approach. MethodsFor the outcomes, we used summary-level data for RA (14 361 people with RA and 43 923 controls) and OA (10 083 people with OA and 40 425 controls) from two genome-wide association studies in European ancestry. For the exposures, five single-nucleotide polymorphisms associated with palmitoleic acid and one associated with oleic acid with genome-wide significance (P < 5 × 10−8) were selected as instrumental variables. The causal effects were estimated using the inverse-variance weighted method with several sensitivity analyses. ResultsFor genetically predicted levels, an increase of one SD in palmitoleic acid (odds ratio, 0.24; 95% confidence interval, 0.10–0.59; P = 0.002) and oleic acid (odds ratio, 0.78; 95% confidence interval, 0.67–0.90; P < 0.001) was significantly associated with lower risk of RA. However, genetic predisposition to either of the two individual MUFAs was not associated with OA risk. Sensitivity analyses yielded similar results. ConclusionsOur Mendelian randomization analyses suggest a causal relationship between higher genetically predicted MUFA levels and lower risks of RA. However, the causality between MUFAs and OA cannot be inferred from this study. Further research is required to unravel the role of MUFA supplementation in arthritis prevention.

Use of dipeptidyl peptidase-4 inhibitors is associated with a lower risk of rheumatoid arthritis in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of cohort studies

Background and aimsCase reports have described occurrence of rheumatoid arthritis (RA) after initiation of Dipeptidyl Peptidase-4 Inhibitors (DPP4i), suggesting a possible adverse effect of the medications. However, the findings from subsequent cohort studies suggest the opposite as they indicate that T2DM patients who used DPP4i tended to have a lower risk of RA. We aimed to investigate the association between use of DPP4i and incident RA in patients with type 2 diabetes mellitus (T2DM) using systematic review and meta-analysis. MethodsPotentially eligible studies were identified from Medline and EMBASE databases from inception to May 2020 using search strategy that comprised of terms for “Dipeptidyl peptidase-4 inhibitor” and “Rheumatoid arthritis”. Eligible study must be cohort study consisting of one cohort of patients with T2DM who were DPP4i users and another cohort of comparators with T2DM who did not receive DPP4i. Then, the study must report effect estimates with 95% confidence intervals (95% CIs) comparing incident RA between DPP4i users versus comparators. Point estimates with standard errors retrieved from each study were combined together using the generic inverse variance method. ResultsA total of 709 articles were identified. After systematic review, four retrospective cohort studies met the eligibility criteria and were included into the meta-analysis. DPP4i users had a significantly lower risk of incident RA compared with comparators with the pooled hazard ratio of 0.72 (95% CI, 0.54–0.96; I2 75%). ConclusionThis systematic review and meta-analysis found a significant association between DPP4i use and a lower risk of incident RA.

Long-term dietary quality and risk of developing rheumatoid arthritis in women

ObjectivesTo evaluate the association between long-term dietary quality, measured by the 2010 Alternative Healthy Eating Index, and risk of rheumatoid arthritis (RA) in women.MethodsWe prospectively followed 76 597 women in...

Acarbose Decreases the Rheumatoid Arthritis Risk of Diabetic Patients and Attenuates the Incidence and Severity of Collagen-induced Arthritis in Mice.

Acarbose has been found to decrease some inflammatory parameters in diabetic patients. This study aimed to examine the influence of acarbose on rheumatoid arthritis (RA) risk in diabetes mellitus (DM) patients and on the incidence and severity of collagen-induced arthritis (CIA) in mice. In a nationwide, matched case–control study, we identified 723 incident RA cases and selected 7,230 age-, sex- and RA diagnosis date–matched controls from all newly treated DM patients. We found that use of acarbose at > 16,950 mg per year was associated with a lower RA risk (odds ratio 0.60; 95% CI, 0.41–0.89). In the CIA mouse study, acarbose was orally administered from days -7 to 38 relative to type II collagen (CII) immunization. The results revealed that acarbose at the dose of 500 mg/kg/day attenuated the incidence and severity of arthritis and the expression of proinflammatory cytokines, including TNF-α, IL-6 and IL-17 in the paw tissues. Acarbose further decreased the productions of anti-CII-IgG, IL-17 and IFN-γ by collagen-reactive lymph node cells. This work suggests that the use of acarbose decreased RA risk in DM patients and the incidence of CIA in mice. Acarbose also attenuated the severity of CIA via anti-inflammatory and immunomodulatory effects.

Breastfeeding and Risk of Rheumatoid Arthritis: A Systematic Review and Metaanalysis.

Previous studies have examined the association between breastfeeding and rheumatoid arthritis (RA), but their results were inconsistent. The aim of this study was to perform a metaanalysis to clarify the effect of breastfeeding on RA risk. The PubMed, EMBASE, Chinese National Knowledge Infrastructure, and Wanfang databases were searched for relevant studies published up to September 10, 2014. Data were extracted, and multivariable-adjusted OR with 95% CI were pooled in the random-effects model. A total of 6 studies were included in the metaanalysis (RA cases: 1672, sample size: 143,670). Overall, an inverse association between breastfeeding and RA was observed (OR 0.675, 95% CI 0.493-0.924, p = 0.014). In the subgroup analysis, decreased RA risk was also found in both breastfeeding 1-12 months (OR 0.783, 95% CI 0.641-0.957, p = 0.015) and breastfeeding > 12 months (OR 0.579, 95% CI 0.462-0.726, p < 0.0005). Sensitivity analysis and cumulative analysis further strengthened the validity of the results. No publication bias was found in this metaanalysis. This metaanalysis suggests that breastfeeding is associated with a lower risk of RA, no matter if breastfeeding time is longer or shorter than 12 months.