Causal associations of plasma omega-3 polyunsaturated fatty acids with sarcopenia-related traits: a two-sample Mendelian randomization study.

OBJECTIVE: To evaluate the causal effect of plasma omega-3 polyunsaturated fatty acids (PUFAs) on sarcopenia-related traits (lean mass, grip strength and walking pace) utilizing two-sample Mendelian randomization (MR) approach. METHODS: Based on genome-wide association study (GWAS) summary statistics, we performed two-sample MR applying the inverse variance weighted (IVW) as the primary method, supplemented with four additional sensitivity analyses. Furthermore, multivariable MR (MVMR) was applied to assess these associations independent of alcohol drinking, type 2 diabetes (T2D), triglycerides (TG), estimated glomerular filtration rate (eGFR) and C-reactive protein (CRP). RESULTS: In univariable MR, the IVW analysis suggested no significant causal effect of genetically determined plasma omega-3 PUFAs on fat-free mass (right leg: ß = 0.01, 95% CI = -0.02 to 0.05, P = 0.375; left leg: ß = 0.01, 95% CI = -0.02 to 0.04, P = 0.446; right arm: ß = 0.01, 95% CI = -0.02 to 0.05, P = 0.376; left arm: ß = 0.01, 95% CI = -0.02 to 0.04, P = 0.384; trunk:ß = 0.02, 95% CI = -0.02 to 0.06, P = 0.283; whole: ß = 0.01, 95% CI = -0.03 to 0.04, P = 0.631), grip strength (right hand: ß = -0.01, 95% CI = -0.03 to 0.01, P = 0.387; left hand: ß = -0.01, 95% CI = -0.02 to 0.01, P = 0.553) and walking pace (ß = 0.00, 95% CI = -0.01 to 0.02, P = 0.575), and sensitive analysis generated similar non-significant results. Furthermore, the MVMR revealed no independent causal association. CONCLUSIONS: Genetically determined plasma omega-3 PUFAs have no causal effect on sarcopenia-related traits.

Relationships Between Inflammatory Parameters Derived From Complete Blood Count and Quantitative Flow Ratio in Patients With Stable Coronary Artery Disease.

To investigate the relationships between inflammatory parameters, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR) and systemic immune-inflammation index (SII), and quantitative flow ratio (QFR) in stable coronary artery disease (CAD) patients (n = 450) enrolled in this cross-sectional study. Logistic regression was performed to evaluate the associations of NLR, PLR, MLR, and SII evaluated as continuous and binary variables with QFR ≤0.80. When treated as continuous variables, lnNLR was associated with QFR ≤0.80 with borderline significance in univariable (odds ratio (OR) = 1.60, p = .05) and multivariable analysis (OR = 1.72, p = .05), while lnMLR was associated with QFR ≤0.80 significantly in univariable analysis (OR = 1.87, p = .03) and with borderline significance in multivariable analysis (OR = 1.91, p = .05). When treated as binary variables, high levels of MLR and SII were significantly associated with QFR ≤0.80 in univariable (MLR: OR = 1.91, p = .02; SII: OR = 2.42, p = .006) and multivariable analysis (MLR: OR = 1.83, p = .04; SII: OR = 2.19, p = .02). NLR, MLR, and SII, but not PLR, were significantly associated with the severity of coronary physiology in stable CAD patients.

Evaluating the causal effect of circulating proteome on the risk of osteoarthritis-related traits.

OBJECTIVES: This study aims to identify circulating proteins that are causally associated with osteoarthritis (OA)-related traits through Mendelian randomisation (MR)-based analytical framework. METHODS: Large-scale two-sample MR was employed to estimate the effects of thousands of plasma proteins on 12 OA-related traits. Additional analyses including Bayesian colocalisation, Steiger filtering analysis, assessment of protein-altering variants and mapping expression quantitative trait loci to protein quantitative trait loci were performed to investigate the reliability of the MR findings; protein-protein interaction, pathway enrichment analysis and evaluation of drug targets were conducted to deepen the understanding and identify potential therapeutic targets of OA. RESULTS: Dozens of circulating proteins were identified to have putatively causal effects on OA-related traits, and a majority of these proteins were either drug targets or considered druggable. CONCLUSIONS: Through MR analysis, we have identified numerous plasma proteins associated with OA-related traits, shedding light on protein-mediated mechanisms and offering promising therapeutic targets for OA.

Diet-derived circulating antioxidants and risk of knee osteoarthritis, hip osteoarthritis and rheumatoid arthritis: a two-sample Mendelian randomization study.

Objective: To examine the causal associations of diet-derived circulating antioxidants with knee osteoarthritis (OA), hip OA, and rheumatoid arthritis (RA) within the two-sample Mendelian randomization (MR) framework. Method: Independent single-nucleotide polymorphisms (SNPs) significantly associated with circulating levels of diet-derived antioxidants (retinol, ß-carotene, lycopene, vitamin C and vitamin E) were extracted as genetic instruments. Summary statistics of genetic instruments associated with knee OA, hip OA, and RA were obtained from corresponding genome-wide association studies (GWASs). The inverse-variance weighted (IVW) was applied as the primary analysis method, with four sensitivity analysis approaches employed to evaluate the robustness of the primary results. Results: Genetically determined per unit increment of absolute circulating levels of retinol was significantly associated with a reduced risk of hip OA [odds ratio (OR) = 0.45, 95% confidence interval (CI) 0.26-0.78, p = 4.43 × 10-3], while genetically determined per unit increase in absolute circulating levels of ß-carotene was suggestively associated with increased risk of RA (OR = 1.32, 95% CI 1.07-1.62, p = 9.10 × 10-3). No other causal association was found. Significant evidence for heterogeneity and pleiotropic outlier was only identified when absolute circulating vitamin C was evaluated as the exposure, whereas all sensitive analysis provided consistently non-significant results. Conclusion: Our results demonstrated that genetically determined lifelong higher exposure to absolute circulating levels of retinol is associated with a decreased risk of hip OA. Further MR study with more genetic instruments for absolute circulating levels of antioxidants are needed to confirm our results.

Quantitative infrapatellar fat pad signal intensity alteration as an imaging biomarker of knee osteoarthritis progression.

OBJECTIVE: To determine the association of quantitative infrapatellar fat pad (IPFP) signal intensity alteration with knee osteoarthritis (OA) progression. METHOD: This study was performed based on the Foundation for the National Institutes of Health OA Biomarkers Consortium study, a nested case-control study consisting of 600 participants. The IPFP signal intensity alterations were quantitatively measured at baseline, 12 months and 24 months. The associations of baseline and time-integrated values over 12 and 24 months of IPFP signal intensity measures with knee OA progression over 48 months were evaluated with adjustment for baseline confounders. RESULTS: The baseline level of clustering effect of high signal intensity (Clustering factor (H)) was predictive of clinically relevant progression (both radiographic and pain progression) (OR 1.22). The time-integrated values of all IPFP signal intensity measures, except for mean value of IPFP signal intensity (Mean (IPFP)) over 24 months (ORs ranging from 1.23 to 1.39) as well was all except for Mean (IPFP) and mean value of IPFP high signal intensity (Mean (H)) over 12 months (ORs ranging from 1.20 to 1.31), were positively associated with clinically relevant progression. When the associations of quantitative IPFP signal intensity measures with radiographic and pain progression were examined separately, more IPFP signal intensity measures with stronger effect sizes were associated with radiographic progression compared with pain progression. CONCLUSION: The associations of short-term alteration in quantitative IPFP signal intensity measures with long-term knee OA progression suggest that these measures might serve as efficacy of intervention biomarkers of knee OA.

Arthritis and incident pulmonary diseases in middle-aged and elderly Chinese: a longitudinal population-based study.

BACKGROUND: The coexistence of arthritis and pulmonary abnormalities has long been observed, but the causal inter-relationships among them are still uncertain especially in elderly adults. METHODS: We extracted data from The China Health and Retirement Longitudinal Study (CHARLS). A total of 7534 participants without chronic lung diseases or/and asthma at the baseline and have complete follow-up information were included. Multivariate Cox proportional hazards models were used to estimate the adjusted hazard ratios (HRs) for developing chronic lung diseases or asthma. We also utilized generalized linear models to examine the association between arthritis and baseline peak expiratory flow (PEF). RESULTS: During 50,615 and 51,975 person-years of follow-up, 629 and 188 participants incident chronic lung diseases and asthma, respectively. Compared to those without arthritis, participants with arthritis had a higher risk of chronic lung diseases (HR = 1.54, 95%CI = 1.31-1.81, P = 1.23 × 10-7) and asthma (HR = 1.70, 95%CI = 1.27-2.28, P = 3.78 × 10-4). Arthritis subjects demonstrated significantly lower PEF than those without arthritis [ß = - 11.85 (95%CI = - 17.56, - 6.14), P = 4.81 × 10-5]. The results were stable after excluding these participates who incident chronic lung diseases or asthma in the first 1 year of follow-up. CONCLUSION: Arthritis increased the risk of pulmonary diseases among middle-aged and elderly Chinese. Early detection and treatment of pulmonary abnormalities among arthritis patients could help decrease the mortality and reduce the global burden of arthritis. Key Points • The coexistence of arthritis and pulmonary abnormalities has long been observed, but whether arthritis status can trigger pulmonary disorders is still uncertain. • Arthritis status are associated with increased risk of pulmonary diseases (chronic lung diseases/asthma) among middle-aged and elderly Chinese. • Early detection and treatment of pulmonary abnormalities among arthritis patients could help decrease the mortality and reduce the global burden of arthritis.

Associations Between microRNA-related Genetic Polymorphisms and Clinical Response to Methotrexate in Chinese Rheumatoid Arthritis Patients.

BACKGROUND: Emerging evidence indicates that microRNA (miRNA)-related genetic polymorphisms are strongly involved in the post-transcriptional regulation of the expression of pharmacokinetics and pharmacodynamics- related genes, therefore contributing to the genetic variability of drug response. OBJECTIVE: To investigate the associations of miRNA-related genetic polymorphisms, including miRNA-5189 rs562929801, miRNA-595 rs4909237, SLCO1A2 rs4149009 and MTHFR rs3737966, and clinical response to methotrexate in Chinese rheumatoid arthritis patients. METHODS: One hundred patients treated with MTX for approximately 3 months were prospectively followed up to evaluate the clinical response according to European League Against Rheumatism (EULAR) good and moderate response, disease activity score in 28 joint counts - erythrocyte sedimentation rate (DAS28-ESR) low disease activity (LDA) and remission (REM), change in DAS28-ESR (ΔDAS28-ESR) and ΔDAS28-ESR > 0.6. Genetic polymorphisms were genotyped utilizing the HI-SNP technology. RESULTS: Of the 100 patients with a mean age of 52.23 ± 12.71 years, 81 patients were female (81.00%). After adjusting potential confounders, the major allele of miRNA-5189 rs562929801 was found to be significantly associated with EULAR response (A/A + A/G versus G/G, RR = 0.81, 95% CI = 0.67-0.99, P = 0.04) and ΔDAS28-ESR > 0.6 under dominant model (A/A + A/G versus G/G, RR = 0.83, 95% CI = 0.71-0.98, P = 0.03). However, nonsignificant evidence was detected for the remaining three miRNA-related genetic polymorphisms in neither univariable analysis nor multivariable analysis. CONCLUSION: Our results indicated that miRNA-5189 rs562929801 was significantly associated with clinical response to MTX, and this association warrants further replication studies with larger sample sizes.

Assessing the causal associations of obstructive sleep apnea with serum uric acid levels and gout: a bidirectional two-sample Mendelian randomization study.

OBJECTIVE: Multiple observational studies have reported the close associations of obstructive sleep apnea (OSA) with serum uric acid (SUA) levels and gout. However, the causal nature and direction remains unclear. METHODS: A bidirectional two-sample Mendelian randomization (MR) study was performed, based on publicly available genome-wide association studies (GWAS) summary statistics, to investigate whether OSA is causally related to SUA levels, gout and vice versa. The inverse-variance weighted (IVW) was used as the primary analysis approach, supplemented with four sensitive analysis methods applied to assess the robustness of the results. Moreover, multivariable MR (MVMR) was utilized to evaluate the independent causal effect of OSA on SUA and gout after adjusting for body mass index (BMI), hypertension, type 2 diabetes (T2D), coronary artery disease (CAD), and chronic kidney disease (CKD). RESULTS: Genetically predicted OSA liability was significantly associated with increased levels of SUA (IVW method: ß = 0.19, 95% CI = 0.11 - 0.26, P = 7.24 × 10-7) and risk of gout [IVW method: odds ratio (OR) = 1.75 95% CI = 1.13 - 2.69, P = 0.01] in univariable MR. The MVMR results suggested that OSA retained its significant association with increased SUA levels, whereas the significant association between OSA and gout was attenuated to null after adjusting for BMI and T2D. No causal effect of OSA on SUA levels and gout was found in the reverse direction. CONCLUSIONS: Our findings suggest that OSA was causally associated with increased levels of SUA, but was not independently associated with gout risk.

Does smoking protect against developing osteoarthritis? Evidence from a genetically informed perspective.

OBJECTIVE: Cumulative evidence from observational studies showed an inverse association between smoking and osteoarthritis (OA), but this association could be confounded by obesity. This study aimed to decipher the causal effect of smoking on osteoarthritis risk from a genetically informed perspective. METHODS: We performed a two-sample univariable and multivariable MR to evaluate the independent effect of smoking on OA risk. Summary-level data were obtained from the largest available genome-wide association studies (GWASs) of smoking initiation, body mass index (BMI) and OA. Genetic variants predicted the exposure were selected as instruments from the respective GWAS. RESULTS: Genetically liability for smoking initiation had an effect estimate consistent with increased risk for overall OA (odds ratio (OR)=1.61, 95% confidence interval (CI)=1.43-1.81, P=7.50 × 10-15), hip OA (OR=1.62, 95%CI=1.29-2.02, P=2.93 × 10-5), knee OA (OR=1.54, 95%CI=1.29-1.84, P =1.80 × 10-6) and hip and/or knee OA (OR=1.56, 95%CI=1.34-1.80, P=3.63 × 10-9), respectively. We also found that genetic liability of BMI was significantly associated with OA risk and the OR per genetically predicted 1 kg/m2 increase of BMI ranged from 2.19 to 2.64. Additionally, multivariate MR analysis revealed a strong evidence for an effect of smoking initiation on the risk of overall OA (OR=1.45, 95%CI=1.31-1.61, P=3.69 × 10-12) and its subtypes after controlling for BMI. CONCLUSION: Our findings support an independent deleterious causal effect for smoking upon OA risk, which further strengthen the importance of smoking cessation interventions and obesity management in the general population, in order to lessen the huge burden of OA in the global aging era.

Associations Between Genetic Polymorphisms Within Transporter Genes and Clinical Response to Methotrexate in Chinese Rheumatoid Arthritis Patients: A Pilot Study.

Purpose: To investigate the associations between genetic polymorphisms within transporter genes and clinical response to methotrexate (MTX) in Chinese rheumatoid arthritis (RA) patients. Patients and Methods: A total of 100 RA patients receiving MTX were prospectively followed up for approximately 3 months to determine the clinical response based on several criteria, including European League Against Rheumatism (EULAR) good and moderate response, disease activity score in 28 joint counts - erythrocyte sedimentation rate (DAS28-ESR) low disease activity (LDA), change in DAS28-ESR (ΔDAS28-ESR) and ΔDAS28-ESR >0.6. Fifty-four single nucleotide polymorphisms (SNPs) within seven transporter genes, including SLC19A1, ABCB1, ABCC1~4 and ABCG2, were genotyped. Results: Multivariable analysis revealed that SLC19A1 rs12659 and rs3788200, ABCC2 rs3740066, rs4148396 and rs717620 were significantly associated with EULAR good and moderate response, and ABCC2 rs3740066 and rs717620 were significantly associated with DAS28-ESR LDA, and ABCB1 rs1128503, rs4148737 and ABCC3 rs2277624, rs4148416 were significantly associated with ΔDAS28-ESR. Moreover, 12 genetic polymorphisms were found to be significantly associated with ΔDAS28-ESR >0.6. With adjustment for corresponding confounders, SLC19A1 TGAA haplotype consisting of rs1051266, rs1131596, rs12659 and rs3788200 was significantly associated with EULAR good and moderate response and ΔDAS28-ESR >0.6 compared with the most common haplotype CAGG. The ABCC2 haplotype TTT composed of rs717620, rs4148396 and rs3740066 was significantly associated with EULAR good and moderate response and ΔDAS28-ESR >0.6 compared with the most common haplotype CCC. Conclusion: Our results highlight the potential of genetic polymorphisms within transporter genes, particularly SLC19A1 and ABCC2, as predictors of clinical response to MTX in Chinese RA patients.

Longitudinal association of infrapatellar fat pad signal intensity alteration with biochemical biomarkers in knee osteoarthritis.

OBJECTIVE: To explore the longitudinal association of quantitative infrapatellar fat pad (IPFP) signal intensity alteration with OA-related biomarkers. METHODS: Eighteen OA-related biochemical biomarkers of 600 knee OA participants in the Foundation for the National Institutes of Health OA Biomarkers Consortium (FNIH) study were extracted. The quantitative IPFP signal intensity measures were acquired based on magnetic resonance imaging, including mean value [Mean (IPFP)] and standard deviation [sDev (IPFP)] of the whole IPFP signal intensity, median value [Median (H)] and upper quartile value [UQ (H)] of high signal intensity, the ratio of volume of high signal intensity to volume of whole IPFP signal intensity [Percentage (H)] and Clustering factor (H). The linear mixed-effect model was applied to determine the longitudinal associations between IPFP signal intensity alteration and biochemical biomarkers over 2 years. RESULTS: All IPFP measures except for Clustering factor (H) were positively associated with urine collagenase-cleaved type II collagen neoepitope (uC2C), urine C-terminal cross-linked telopeptide of type II collagen (uCTX-II), urine C-terminal cross-linked telopeptide of type I collagen-α (uCTX-Iα) and urine N-terminal cross-linked telopeptide of type I collagen (uNTX-I). Mean (IPFP), Median (H) and Percentage (H) were positively associated with the nitrated form of an epitope located in the triple helix of type II collagen (Coll2-1 NO2). Mean (IPFP), Median (H) and UQ (H) were positively associated with sCTX-I and uCTX-Iß. Positive associations between sDev (IPFP), Percentage (H) and serum hyaluronic acid (sHA) were found. CONCLUSION: Our results suggest a role of IPFP signal intensity alteration in joint tissue remodelling on a molecular level.

Novel insight into the aetiology of rheumatoid arthritis gained by a cross-tissue transcriptome-wide association study.

BACKGROUND: Although genome-wide association studies (GWASs) have identified more than 100 loci associated with rheumatoid arthritis (RA) susceptibility, the causal genes and biological mechanisms remain largely unknown. METHODS: A cross-tissue transcriptome-wide association study (TWAS) using the unified test for molecular signaturestool was performed to integrate GWAS summary statistics from 58 284 individuals (14 361 RA cases and 43 923 controls) with gene-expression matrix in the Genotype-Tissue Expression project. Subsequently, a single tissue by using FUSION software was conducted to validate the significant associations. We also compared the TWAS with different gene-based methodologies, including Summary Data Based Mendelian Randomization (SMR) and Multimarker Analysis of Genomic Annotation (MAGMA). Further in silico analyses (conditional and joint analysis, differential expression analysis and gene-set enrichment analysis) were used to deepen our understanding of genetic architecture and comorbidity aetiology of RA. RESULTS: We identified a total of 47 significant candidate genes for RA in both cross-tissue and single-tissue test after multiple testing correction, of which 40 TWAS-identified genes were verified by SMR or MAGMA. Among them, 13 genes were situated outside of previously reported significant loci by RA GWAS. Both TWAS-based and MAGMA-based enrichment analyses illustrated the shared genetic determinants among autoimmune thyroid disease, asthma, type I diabetes mellitus and RA. CONCLUSION: Our study unveils 13 new candidate genes whose predicted expression is associated with risk of RA, providing new insights into the underlying genetic architecture of RA.

Association of serum levels of inflammatory markers and adipokines with joint symptoms and structures in participants with knee osteoarthritis.

OBJECTIVE: To investigate the longitudinal associations of serum inflammatory markers and adipokines with joint symptoms and structures in participants with knee OA. METHODS: Two hundred participants (46.5% female, mean age 63.1 years, mean BMI 29.5 kg/m2) from Tasmania, part of the VIDEO (Vitamin D Effect on OA) study, were randomly selected in the current study. Serum levels of 19 biomarkers, scores of WOMAC and MRI-assessed knee structures were evaluated at baseline and month 24. The patterns of biomarkers were derived from principal component analysis and their association with knee symptoms and structures were examined using adjusted generalized estimating equations. RESULTS: Five components explained 78% of the total variance. IL-1ß, -2, -4, -6, -8, -17 A, -17 F, -21, -22 and -23 loaded the highest on the first component, which was associated with increased bone marrow lesions (BMLs) and WOMAC dysfunction score. IL-10, -12 and GM-CSF loaded on the second component, which was associated with increased cartilage volume, and decreased effusion synovitis and WOMAC scores. Leptin, adipsin and CRP loaded on the third component, which was positively associated with WOMAC scores. Resistin loaded on the fourth component, which was associated with increased BMLs and cartilage defects. Apelin-36 and adiponectin loaded on the fifth component, which was associated with increased BMLs. CONCLUSION: Various inflammatory and metabolic components were associated differently with joint symptoms and structural changes in knee OA, suggesting a complex inflammatory and metabolic interrelationship in the pathogenesis of knee OA.

Assessment of genetic polymorphisms within nuclear factor-κB signaling pathway genes in rheumatoid arthritis: Evidence for replication and genetic interaction.

OBJECTIVE: This study was performed to replicate the associations of genetic polymorphisms within nuclear factor-κB (NF-κB) signaling pathway genes with rheumatoid arthritis (RA), and to further examine genetic interactions in a Chinese population. METHODS: A total of eleven single-nucleotide polymorphisms (SNPs) were genotyped in 594 RA patients and 604 healthy controls. RESULTS: Genetic association analysis revealed that NFKBIE rs2233434, TNIP1 rs10036748 and BLK rs13277113 were significantly associated with RA, cyclic citrullinated peptide (CCP)-positive RA and rheumatoid factor (RF)-positive RA, and TNFAIP3 rs2230926 was significantly associated with CCP-positive RA. Significant additive interaction was observed between NFKB1 rs28362491 and IKBKE rs12142086 (RERI = 0.76, 95% CI 0.13-1.38; AP = 0.57, 95% CI 0.11-1.03), NFKBIE rs2233434 and BLK rs13277113 (RERI = 1.41, 95% CI 0.88-1.94; AP = 0.85, 95% CI 0.50-1.20), NFKBIL rs2071592 and TNIP1 rs10036748 (RERI = 0.59, 95% CI 0.17-1.02; AP = 0.46, 95% CI 0.05-0.87), UBE2L3 rs5754217 and TNFSF4 rs2205960 (RERI = 0.50, 95% CI 0.16-0.84; AP = 0.57, 95% CI 0.09-1.05). Significant multiplicative interaction was detected between BLK rs13277113 and UBE2L3 rs5754217 (p = 0.02), BLK rs13277113 and TNFSF4 rs2205960 (p = 0.03). CONCLUSIONS: Our results lent further support to the role of NF-κB signaling pathway in the pathogenesis of RA from a genetic perspective.

Associations between diet quality and knee joint structures, symptoms and systemic abnormalities in people with symptomatic knee osteoarthritis.

BACKGROUND & AIMS: The evidence of benefiting from a high-quality diet for knee osteoarthritis (OA) joint structures, symptoms, and systemic abnormalities is limited. Clarifying the relationship between diet quality and knee OA could provide useful information for knee OA management. To investigate the associations between diet quality and knee joint structures, symptoms, lower limb muscle strength, depressive symptoms, and quality of life in people with knee OA. METHODS: This study was a post-hoc, exploratory analysis using data from a randomized controlled trial in symptomatic knee OA participants with a follow-up time of 24 months. In brief, eligible participants of the original study were aged 50-79 years, had symptomatic knee OA, and had a pain of 20-80 mm on a 100-mm visual analog scale. After excluding the patients without information on diet quality, 392 participants were included in this post-hoc analysis. Diet quality was assessed at baseline using the Australian Recommended Food Score (ARFS) which includes subscores of vegetable, fruit, grain, dairy products, fat, and alcohol. Knee joint structures (including cartilage volume, cartilage defect, bone marrow lesions, and effusion-synovitis volume assessed by magnetic resonance imaging), OA symptoms, lower limb muscle strength, depressive symptoms, and quality of life were assessed at baseline and follow up. Mixed-effects models were used to assess the associations of diet quality with those outcomes. RESULTS: Diet quality mainly reflect diet variety within the core food was not associated with knee structures and OA symptoms, but was associated with greater lower limb muscle strength (ß = 0.66, P = 0.001), lower depressive symptom (ß = -0.08, P = 0.001), and better quality of life (ß = -0.06, P = 0.002). In further analyses of food group-based sub-scores, only the vegetable sub-score had the similar associations with lower limb muscle strength (ß = 1.03, P = 0.004), depressive symptom (ß = -0.17, P < 0.001), and quality of life (ß = -0.14, P < 0.001). CONCLUSIONS: Higher diet quality, mainly vegetable diet quality, is associated with greater lower limb muscle strength, less depressive symptoms, and higher quality of life in knee OA patients, suggesting higher diet quality may have protective effects on knee OA.

Associations of blood pressure and arterial stiffness with knee cartilage volume in patients with knee osteoarthritis.

OBJECTIVE: To describe the associations of blood pressure and arterial stiffness with knee cartilage volume in patients with knee OA. METHODS: A secondary analysis was performed on the data from participants in a randomized controlled trial that identified the effects of vitamin D supplementation on knee structures and symptoms among patients with symptomatic knee OA. Brachial and central blood pressure, arterial stiffness indicators and knee cartilage volume were measured at baseline and the 2 year follow-up. Associations were assessed using generalized estimating equations. RESULTS: Among 231 participants (average age 63.2 years), 48.9% were females. Higher supine systolic and diastolic pressures were significantly associated with lower tibial cartilage volume (systolic: lateral ß -6.23, medial ß -5.14, total ß -11.35 mm3/mmHg; diastolic: lateral ß -10.25, medial ß -11.29, total ß -21.50 mm3/mmHg). Higher supine systolic pressure was associated with lower femoral cartilage volume (lateral ß -17.35, total ß -28.31 mm3/mmHg). Central systolic pressure and arterial stiffness indicators (including pulse wave velocity, central pulse pressure and peripheral pulse pressure) were largely not associated with knee cartilage volume; however, higher augmentation index was associated with lower tibial and femoral cartilage volume (tibial: medial ß -8.24, total ß -19.13 mm3/%; femoral: lateral ß -23.70, medial ß -26.42, total ß -50.12 mm3/%). CONCLUSIONS: Blood pressure and arterial stiffness are associated with knee cartilage volume at several sites in knee OA patients. This supports that blood pressure and arterial stiffness may involve in the progression of knee OA.

Genetic association analysis of ATG16L1 rs2241880, rs6758317 and ATG16L2 rs11235604 polymorphisms with rheumatoid arthritis in a Chinese population.

OBJECTIVE: This study was performed to test whether ATG16L1 rs2241880, rs6758317 and ATG16L2 rs11235604 polymorphisms were associated with RA and further examine the genetic interaction between ATG16L1 and ATG16L2 in RA among a Chinese population. METHODS: A total of 594 RA patients and 604 healthy controls were included, and the genetic polymorphisms were genotyped based on HI-SNP technology. RESULTS: Significant associations of ATG16L1 rs2241880 polymorphism with RA (T/T versus C/T + C/C, OR = 1.32, 95% CI 1.04-1.67, P = 0.02), cyclic citrullinated peptide (CCP)-positive RA (genotype comparison, P = 5.38 × 10-3; T/T versus C/T + C/C, OR = 1.45, 95% CI 1.12-1.87, P = 4.86 × 10-3) and rheumatoid factor (RF)-positive RA (genotype comparison, P = 0.03; T versus C, OR = 1.23, 95% CI 1.01-1.49, P = 0.04; T/T versus C/T + C/C, OR = 1.44, 95% CI 1.10-1.88, P = 7.62 × 10-3) were found. Significant genetic interaction between ATG16L1 rs2241880 and ATG16L2 rs11235604 was associated RA (P = 0.03), and significant genetic interaction between ATG16L1 rs6758317 and ATG16L2 rs11235604 was associated with RA (P = 7.57 × 10-3), CCP-positive RA (P = 0.01) and RF-positive RA (P = 0.01). Consistently, stratification analysis found that significant associations of RA with ATG16L1 rs2241880, rs6758317 polymorphisms were only detected among individuals carrying C/T genotype of the ATG16L2 rs11235604 polymorphism. CONCLUSIONS: Our results indicated that ATG16L1 rs2241880 polymorphism was associated with RA in Chinese population, and provided evidence for genetic interaction between ATG16L1 and ATG16L2 in determing the development of RA, highlighting the involvement of autophagy in the pathogenesis of RA.

Associations of genetic polymorphisms within MALAT1, UCA1, FAM211A-AS1 and AC000111.6 with genetic susceptibility to rheumatoid arthritis.

Recently, several long non-coding RNAs (lncRNAs) including MALAT1, UCA1, ENST00000483588, and ENST00000456270 have been implicated in the pathogenesis of rheumatoid arthritis (RA), and we hypothesized that polymorphisms within these lncRNA genes might be genetic modifiers for the development of RA. A total of 10 potentially functional single-nucleotide polymorphisms (SNPs) were selected and genotyped in 1198 participants, including 594 RA patients and 604 healthy controls. Significant associations of FAM211A-AS1 rs2882581 (G vs. A, OR = 1.31, 95%CI 1.07-1.62, p = .01; G/G + A/G vs. A/A, OR = 1.40, 95%CI 1.08-1.83, p = .01), rs3744281 (T vs. A, OR = 1.25, 95%CI 1.02-1.54, p = .03; T/T vs. A/T + A/A, OR = 1.69, 95%CI 1.01-2.82, p = 4.59 × 10-2), and rs3760235 (A vs. G, OR = 1.32, 95%CI 1.04-1.68, p = .02; A/A vs. A/G + G/G, OR = 1.32, 95%CI 1.00-1.74, p = 4.89 × 10-2) with RF-positive RA were found. Functional annotation results indicated that these identified polymorphisms might regulate the expression of FAM211A-AS1 and nearby genes via impacting on transcription factor binding. Taken together, our results indicated that FAM211A-AS1 rs2882581, rs3744281, and rs3760235 were involved in the genetic background of RF-positive RA.

Associations of TRAF1/C5 rs10818488 and rs3761847 polymorphisms with genetic susceptibility to rheumatoid arthritis: a case-control study and updated meta-analysis.

The results on associations of tumor necrosis factor (TNF)-receptor associated factor 1/complement component 5 (TRAF1/C5) rs10818488 and rs3761847 polymorphisms with rheumatoid arthritis (RA) are controversial, thus this study was performed to examine whether the aforementioned polymorphisms were associated with RA in a Chinese population. Furthermore, an updated meta-analysis was conducted. The polymorphisms were genotyped in 328 Chinese RA patients and 449 healthy controls. Studies examining the association of TRAF1/C5 rs10818488 and/or rs3761847 polymorphism with RA were exhaustively searched. No significant difference in either genotype or allele distribution between RA patients and controls was found. The updated meta-analysis was conducted based on 19 articles including the present study. A significant association of RA with TRAF1/C5 rs10818488 polymorphism G allele in Europeans (OR = 0.843, 95% CI = 0.730-0.975, p = 0.021) and in Asians (OR = 1.070, 95% CI = 1.009-1.136, p = 0.024) was found. Additionally, a significant association of RA with TRAF1/C5 rs10818488 polymorphism G allele under the recessive model in Asians (OR = 1.129, 95% CI = 1.023-1.246, p = 0.016) and in Africans (OR = 0.657, 95% CI = 0.507-0.851, p = 0.001) was found. Only a borderline significant association of RA with TRAF1/C5 rs3761847 polymorphism A allele was found in Europeans. Non-significant associations of RA with TRAF1/C5 rs10818488 and rs3761847 polymorphisms were found in our study. The updated meta-analysis results demonstrate that TRAF1/C5 rs10818488 polymorphism is associated with RA in Europeans, Asians and Africans, and TRAF1/C5 rs3761847 polymorphism is associated with RA in Europeans with borderline significant evidence.