scholarly journals O27 Frailty and co-morbidity in people with osteoarthritis and rheumatoid arthritis

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Michael J Cook ◽  
Mark Lunt ◽  
Suzanne M M Verstappen ◽  
Terence W O'Neill
Keyword(s):  
Rheumatoid Arthritis ◽  
Relative Risk ◽  
Multinomial Logistic Regression ◽  
Smoking Status ◽  
Relative Risk Ratio ◽  
Chronic Obstructive ◽  
Biological Interaction ◽  
Frailty Phenotype ◽  
Increased Risk ◽  
Co Morbidity

Abstract Background/Aims  People with osteoarthritis (OA) and rheumatoid arthritis (RA) are at increased risk of frailty, though the role of co-morbidities in contributing to frailty risk in these arthritides is uncertain. The aim of this study was i) to determine the association between common co-morbidities and frailty in OA and RA; and ii) to determine whether co-morbidities interact synergistically with OA and RA to increase the likelihood of frailty. Methods  A cross-sectional analysis of the UK Biobank data was carried out. In this national cohort of participants aged 40-69 years, self-reported physician-diagnosed diseases including OA, RA, and common co-morbidities (including hypertension, coronary heart disease, diabetes, stroke/TIA, chronic obstructive pulmonary disease (COPD), and depression) were recorded. Frailty was assessed using a modification of the frailty phenotype (FP), comprising five components: self-reported weight loss, exhaustion, low physical activity (international activity questionnaire), slow walking speed, and low hand-grip strength. Pre-frailty and frailty, was identified based on the presence of 1-2 and ≥3 of these components, respectively. Among participants with OA and RA at baseline, the likelihood of being pre-frail or frail (vs not frail) at baseline among people with (vs without) each of the co-morbidities was assessed using multinomial logistic regression. To determine whether co-morbidities interact synergistically with OA and RA to increase the likelihood of frailty, deviation from additivity of risk was estimated by calculating the attributable proportion (AP) of risk due to biological interaction. An AP > 0 indicates positive (synergistic) biological interaction. Analyses were adjusted for age, sex, smoking status, BMI, and deprivation. Results  In total, 457,561 people were included in the analysis; 35,884 (7.8%) had OA and 4,894 (1.1%) had RA. Overall, the mean (SD) age was 56.5 (8.1) years and 54% were female. The overall prevalence of frailty was 3.4%. The prevalence of frailty was higher among those with OA (10.0%) and RA (18.6%). Each of the co-morbidities considered was associated with increased relative risk of pre-frailty and frailty particularly COPD in OA, relative risk ratio (95%CI): pre-frailty, 2.09 (1.80, 2.42) and frailty, 4.45 (3.71, 5.33) and stroke/TIA in RA: pre-frailty, 1.97 (1.18, 3.29) and frailty, 3.64 (2.11, 6.29). Most of the co-morbidities considered interacted synergistically with OA and RA to increase the risk of pre-frailty and frailty, particularly diabetes in OA, AP (95% CI): pre-frailty, 0.13 (0.04, 0.23) and frailty, 0.49 (0.42, 0.55) and stroke/TIA in RA: pre-frailty, 0.34 (0.003, 0.68) and frailty 0.60 (0.38, 0.82). Conclusion  Co-morbidity is associated with an increased occurrence of pre-frailty and frailty among people with OA and RA and interacts synergistically with OA and RA to increase the likelihood of pre-frailty and frailty. Disclosure  M.J. Cook: None. M. Lunt: None. S.M.M. Verstappen: None. T.W. O'Neill: None.

Policy Changes and Child Blood Lead Levels by Age 2 Years for Children Born in Illinois, 2001–2014

2020 ◽  
Vol 110 (5) ◽  
pp. 734-740
Author(s):  
Ali Abbasi ◽  
Bridget Pals ◽  
Ludovica Gazze
Keyword(s):  
Relative Risk ◽  
Multinomial Logistic Regression ◽  
Lead Level ◽  
Blood Lead ◽  
Relative Risk Ratio ◽  
Intervention Threshold ◽  
Industrial Emissions ◽  
Screening Guidelines ◽  
Increased Risk ◽  
Lead Testing

Objectives. To evaluate how lowering the blood lead level (BLL) intervention threshold affects childhood lead testing policy. Methods. We geocoded 4.19 million Illinois lead testing records (2001–2016) and linked to 2.37 million birth records (2001–2014), data on housing age, industrial emissions, and roads. We used multinomial logistic regression to determine predictors of BLLs of 10 micrograms per deciliter (µg/dL) or greater, 5 to 9 µg/dL, and 4 µg/dL. Results. We found that 2.2% of children had BLLs of 10 µg/dL or greater, 8.9% had BLLs of 5 to 9 µg/dL, and 5.7% had BLLs of 4 µg/dL. Pre-1930 housing was associated with more than 2- to 4-fold increased relative risk of BLLs above all thresholds. Housing built in 1951 to 1978 was associated with increased relative risk of BLLs of 5 to 9 µg/dL (relative risk ratio [RRR] = 1.14; 95% confidence interval [CI] = 1.06, 1.21) but not with increased relative risk of BLLs of 10 µg/dL or greater (RRR = 0.99; 95% CI = 0.84, 1.16). At a given address, previous BLLs of 5 to 9 µg/dL or BLLs of 10 µg/dL or greater were associated with increased risk of BLLs of 5 to 9 µg/dL or BLLs of 10 µg/dL or greater among current occupants by 2.37- (95% CI = 2.20, 2.54) fold and 4.08- (95% CI = 3.69, 4.52) fold, respectively. Conclusions. The relative importance of determinants of above-threshold BLLs changes with decreasing intervention thresholds. Public Health Implications. States may need to update lead screening guidelines when decreasing the intervention threshold.

scholarly journals A krónikus obstruktív tüdőbetegség metabolikus következményei

2021 ◽  
Vol 162 (5) ◽  
pp. 185-191
Author(s):  
Mónika Fekete ◽  
Vince Fazekas-Pongor ◽  
Gergő Szőllősi ◽  
János Tamás Varga
Keyword(s):  
Quality Of Life ◽  
Metabolic Syndrome ◽  
Lung Function ◽  
Smoking Status ◽  
International Diabetes Federation ◽  
Walking Distance ◽  
Chronic Obstructive ◽  
Copd Patients ◽  
Co Morbidity

Összefoglaló. Bevezetés: Krónikus obstruktív tüdőbetegségben (COPD) az obesitas mellett a csökkent fizikai aktivitás nagymértékben fokozza a metabolikus szindróma kialakulásának valószínűségét. Célkitűzés: Kutatásunk célja volt felmérni a metabolikus szindróma prevalenciáját COPD-ben, valamint azt, hogy milyen mértékben függ össze az életkorral, a nemmel, a társbetegségekkel, a tüdőfunkció károsodásának mértékével, a tápláltsági állapottal, a fizikai terhelhetőséggel és az életminőséggel. Módszer: Keresztmetszeti vizsgálatot végeztünk az Országos Korányi Pulmonológiai Intézet Légzésrehabilitációs Osztályán fekvő betegek körében 2019. július 1. és december 31. között. A véletlenszerűen kiválasztott 300, 40 év feletti betegnek ismertük az antropometriai, légzésfunkciós vizsgálati eredményét és laboratóriumi paramétereit. Adatokat gyűjtöttünk a dohányzási szokásokról, az előző évi exacerbatiók számáról és a kortikoszteroidok használatáról is. Az életminőség mérésére a betegségspecifikus Szent György-féle Légzési Kérdőív magyar nyelvre validált változatát használtuk. A metabolikus szindrómát a Nemzetközi Diabetes Szövetség kritériumai alapján határoztuk meg. Eredmények: A metabolikus szindróma a betegek 72%-ánál fordult elő, férfi: 65,9% nő: 77,2% (p = 0,031). A metabolikus szindrómás betegek esetében rövidebb 6 perces sétatávolságot mértünk ([m] 250 [150–330] vs. 295 [162–360]; p = 0,384), és szignifikánsan több volt az előző évi exacerbatiók száma (3 [0–6] vs. 1 [1–2]; p<0,001) a nem metabolikus szindrómás betegekhez képest. A BMI-re történő stratifikáció után a metabolikus szindróma jelenléte nagyobb volt BMI≥25 kg/m2 esetén. A hasi elhízás, a magas vérnyomás, a hyperlipidaemia és a hyperglykaemia szignifikánsan gyakoribb volt BMI≥25 kg/m2 esetén (p<0,001). Következtetés: Eredményeink azt sugallják, hogy a metabolikus szindrómás betegekben megnő az együttes morbiditási index, különösen azok körében, akik túlsúlyosak vagy elhízottak. Ezért a COPD-s betegekben nagyon fontos időben felismerni és megfelelően kezelni a metabolikus szindrómát. Orv Hetil. 2021; 162(5): 185–191. Summary. Introduction: Both obesity and the lack of physical activity among chronic obstructive pulmonary disease (COPD) patients increase the risk of developing metabolic syndrome. Objective: The goal of our study was to assess the prevalence of metabolic syndrome among COPD patients and to examine its correlation with age, gender, comorbidities, lung function values, nutritional status, exercise capacity, and quality of life. Method: A cross-sectional study was performed at the Department of Pulmonary Rehabilitation of the Hungarian National Korányi Institute for Pulmonology between July 1st and December 31st, 2019. A total of 300 patients aged over 40 were selected at random. Anthropometric data were collected along with lung function values, laboratory parameters, smoking status, the number of exacerbations in the previous year, and the use of corticosteroids. Quality of life was measured by the validated Hungarian, COPD-specific Saint George Respiratory Questionnaire. Metabolic syndrome was defined according to the International Diabetes Federation criteria. Results: Metabolic syndrome affected 72% of COPD patients (male: 65.9%, female 77.2%; p = 0.031). In patients with metabolic syndrome, shorter 6-minute walking distance was measured ([m] 250 [150–330] vs. 295 [162–360]; p = 0.384) and the number of exacerbations in the previous year was significantly higher (3 [0–6] vs. 1 [1–2]; p<0.001) compared to patients with no metabolic syndrome. After stratification for BMI, metabolic syndrome was more frequent in the case of BMI≥25 kg/m2. Central adiposity, hypertension, hyperlipidemia, and hyperglycemia were also significantly more frequent among patients with BMI≥25 kg/m2 (p<0.001). Conclusion: Our results suggest that the co-morbidity index increases in patients with metabolic syndrome, especially in overweight or obese patients. Therefore, early detection and appropriate treatment of metabolic syndrome in patients with COPD is very important. Orv Hetil. 2021; 162(5): 185–191.

scholarly journals Cleaning products and respiratory health outcomes in occupational cleaners: a systematic review and meta-analysis

2020 ◽  
pp. oemed-2020-106776
Author(s):  
Olia Archangelidi ◽  
Sean Sathiyajit ◽  
Dario Consonni ◽  
Debbie Jarvis ◽  
Sara De Matteis
Keyword(s):  
Systematic Review ◽  
Relative Risk ◽  
Health Effects ◽  
Respiratory Health ◽  
Meta Analysis ◽  
Atopic Asthma ◽  
Chronic Obstructive ◽  
Lung Function Decline ◽  
Cleaning Products ◽  
Increased Risk

There is consistent evidence of increased respiratory symptoms in occupational cleaners; however, uncertainty remains on type of respiratory health effects, underlying causal agents, mechanisms and respiratory phenotypes. We aimed to conduct a systematic review and if possible, a meta-analysis of the available literature to characterise and quantify the cleaning-related respiratory health effects. We searched MEDLINE and EMBASE databases and included studies that evaluated the association of any respiratory health outcome with exposure to cleaning occupation or products in occupational cleaners. A modified GRADE was used to appraise the quality of included studies. We retrieved 1124 articles, and after applying our inclusion criteria, 39 were selected for the systematic review. We performed a meta-analysis of the 21 studies evaluating asthma which showed a 50% increased pooled relative risk in cleaners (meta-relative risk (RR)=1.50; 95% CI 1.44 to 1.56). Population-based cross-sectional studies showed more stable associations with asthma risk. No evidence of atopic asthma as dominant phenotype emerged. Also, we estimated a 43% increased risk (meta-RR=1.43; 95% CI 1.31 to 1.56) of chronic obstructive pulmonary disease. Evidence for associations with bronchial-hyper-responsiveness, lung function decline, rhinitis, upper and lower respiratory tract symptoms was weaker. In our systematic review and meta-analysis, we found that working as a cleaner is associated with an increased risk of reversible and even irreversible obstructive airway diseases. All studies lacked quantitative exposure assessment to cleaning products; this would help elucidate underlying causal agents and mechanisms. Exposure control and respiratory surveillance among cleaners is warranted to prevent the associated respiratory health burden. Trial registration number: CRD4201705915.

scholarly journals The multifaceted impact of anxiety and depression on patients with rheumatoid arthritis

2019 ◽  
Vol 3 (1) ◽  
Author(s):  
Steve Peterson ◽  
James Piercy ◽  
Stuart Blackburn ◽  
Emma Sullivan ◽  
Chetan S. Karyekar ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Multinomial Logistic Regression ◽  
The United States ◽  
Anxiety And Depression ◽  
Relative Risk Ratio ◽  
Depression Symptoms ◽  
Patient Anxiety ◽  
Patient Reported ◽  
The Usa ◽  
The Impact

Abstract Background The prevalence of mood disturbances such as anxiety and depression is greater in rheumatoid arthritis (RA) patients than in the general population. Given this association, the primary aim of this study was to assess the incremental impact of anxiety or depression on patients with RA from the United States of America (USA) and Europe, independent of the impact of the underlying RA disease. Methods Rheumatologists (n = 408) from the USA and 5 European countries completed patient record forms for a predetermined number of RA patients who consulted consecutively during the study period; these patients completed patient-reported questionnaires. Descriptive statistics and multivariate regression were used to investigate the relationship between anxiety and depression with treatment and economic outcomes in RA patients. Results Of 1015 physician and patient pairs who completed all relevant questionnaire sections, 390 (38.4%) patients self-reported anxiety or depression, while 180 (17.7%) patients were reported to have anxiety or depression by their physicians. Controlling for age, gender, body mass index and clinical factors (flaring and severity), multiple regression analyses suggested that patients with anxiety or depression more often experienced treatment dissatisfaction (odds ratio [OR] 2.28; P < .001), had greater impairment in work (coefficient [β] = 11.82; P = .001) and usual activity (β = 14.73; P < .001), greater disability (β = .35; P < .001), and more often reported unemployment (OR 1.74; P = .001). Multinomial logistic regression revealed discordance between physician and patient satisfaction with treatment. For patients reporting anxiety or depression, physicians were more often satisfied with achievement of current disease control than patients (relative risk ratio 2.19; P = .002). Conclusion Concomitant anxiety or depression was associated with a significant incremental impact on the health-related quality of life and economic aspects of life of patients with RA. In light of observed differences between physician recognition of patient anxiety and/or depression versus patient reporting of anxiety and/or depression symptoms, further research is warranted to develop optimal screening and management of depression and anxiety in patients with RA.

scholarly journals Interaction between asthma and smoking increases the risk of adult airway obstruction

2014 ◽  
Vol 45 (3) ◽  
pp. 635-643 ◽  
Author(s):  
Marianne Aanerud ◽  
Anne-Elie Carsin ◽  
Jordi Sunyer ◽  
Julia Dratva ◽  
Thorarinn Gislason ◽  
...  
Keyword(s):  
Airway Obstruction ◽  
Early Onset ◽  
Linear Models ◽  
Late Onset ◽  
Smoking Status ◽  
Random Effect ◽  
Chronic Obstructive ◽  
Lung Function Decline ◽  
Increased Risk ◽  
Never Smokers

The aim of the present study was to analyse the interaction between asthma and smoking in the risk of adult airway obstruction, accounting for atopy.In the European Community Respiratory Health Survey, 15 668 persons aged 20–56 years underwent spirometry in 1991–1993 and 9 years later (n=8916). Risk of airway obstruction and lung function decline associated with smoking and early-onset (<10 years of age) and late-onset (>10 years of age) asthma were analysed with generalised estimating equation models and random-effect linear models, adjusting for covariates. Interaction of asthma with smoking was expressed as relative excess risk due to interaction (RERI).A 20-fold increase in adult airway obstruction was found among those with early-onset asthma independently of smoking status (never-smokers: OR 21.0, 95% CI 12.7–35; current smokers: OR 23.7, 95% CI 13.9–40.6). Late-onset asthma was associated with airway obstruction, with a stronger association among current smokers (OR 25.6, 95% CI 15.6–41.9) than among never-smokers (OR 11.2, 95% CI 6.8–18.6) (RERI 12.02, 95% CI 1.96–22.07). Stratifying by atopy, the association between smoking and asthma was most pronounced among nonatopics.Early- and late-onset asthma were associated with 10–20-fold increased risk of adult airway obstruction. Smoking increased the risk of adult airway obstruction in subjects with asthma onset after age 10 years. Investigation of measures potentially preventive of chronic obstructive pulmonary disease development following asthma is urgently needed.

scholarly journals Widespread Sexual Dimorphism in the Transcriptome of Human Airway Epithelium in Response to Smoking

2019 ◽  
Author(s):  
Chen Xi Yang ◽  
Henry Shi ◽  
Irving Ding ◽  
Cheng Wei Tony Yang ◽  
Edward Kyoo-Hoon Kim ◽  
...  
Keyword(s):  
Airway Epithelium ◽  
Molecular Mechanisms ◽  
Smoking Status ◽  
Epidemiological Studies ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Human Airway ◽  
Human Airway Epithelium ◽  
Increased Risk ◽  
Former Smokers

ABSTRACTEpidemiological studies have shown that female smokers are at higher risk of chronic obstructive pulmonary disease (COPD). Female patients have worse symptoms and health status and increased risk of exacerbations. We determined the differences in the transcriptome of the airway epithelium between males and females at baseline and in response to smoking. We processed public gene expression data of human airway epithelium into a discovery cohort of 211 subjects (never smokers n=68; current smokers n=143) and two replication cohorts of 104 subjects (21 never, 52 current, and 31 former smokers) and 238 subjects (99 current and 139 former smokers. We analyzed gene differential expression with smoking status, sex, and smoking-by-sex interaction and used network approaches for modules’ level analyses. We identified and replicated two differentially expressed modules between the sexes in response to smoking with genes located throughout the autosomes and not restricted to sex chromosomes. The two modules were enriched in autophagy (up-regulated in female smokers) and response to virus and type 1 interferon signaling pathways which were down-regulated in female smokers compared to males. The results offer insights into the molecular mechanisms of the sexually dimorphic COPD risk and presentation potentially enabling a precision medicine approach to COPD.

514 FRAILTY IN OSTEOARTHRITIS AND THE INFLUENCE OF CO-MORBIDITY

2021 ◽  
Vol 50 (Supplement_2) ◽  
pp. ii5-ii7
Author(s):  
M J Cook ◽  
S M M Verstappen ◽  
M Lunt ◽  
T W O’Neill
Keyword(s):  
Physical Activity ◽  
Grip Strength ◽  
Negative Binomial ◽  
Adjusted Relative Risk ◽  
Additive Interaction ◽  
Frailty Phenotype ◽  
Attributable Proportion ◽  
Physical Measurements ◽  
Increased Risk ◽  
Co Morbidity

Abstract Introduction Risk factors for frailty, including low physical activity and chronic pain, are common among people with osteoarthritis. The aim of this analysis was to determine the association between osteoarthritis and frailty and to determine whether comorbidities interact additively with OA to increase the likelihood of frailty. Methods Men and women aged 40-69 years who contributed to the UK Biobank were analysed. Data about self-reported physician-diagnosed diseases was collected, as well physical measurements, including hand-grip strength. Frailty (robust, pre-frail, frail) was assessed using a modified frailty phenotype, comprising five components: low grip strength, slow walking speed, weight loss, low physical activity, and exhaustion. The association between osteoarthritis and the frailty phenotype was determined using negative binomial regression, adjusting for age, sex, body mass index, smoking status, and Townsend deprivation score. We calculated the attributable proportion of risk of frailty due to additive interaction between osteoarthritis and common co-morbidities (cardiovascular disease, diabetes, COPD, and depression). Results 457,561 people were included, 35,884 (7.8%) had osteoarthritis. The adjusted relative risk ratio (95% CI) for pre-frailty and frailty (versus robust), respectively was higher among people with (versus without) osteoarthritis: 1.58 (1.54, 1.62) and 3.41 (3.26, 3.56). There was significant additive interaction between the presence of osteoarthritis and each of the co-morbidities considered in increasing risk of frailty, particularly diabetes (attributable proportion of risk due to additive interaction with osteoarthritis (95% CI)), 0.49 (0.42, 0.55), coronary heart disease 0.48 (0.41, 0.55), and depression 0.47 (0.41, 0.53). Conclusions Our results suggest that people with OA are at increased risk of pre-frailty and frailty. The mechanisms are not fully understood, though co-morbidity appears to contribute to the risk of frailty beyond the expected additivity of risk due to OA and co-morbidity. Early diagnosis and optimal management of co-morbidities in people with OA may be beneficial.

scholarly journals The problem of accelerated atherosclerosis in systemic lupus erythematosus: Insights into a complex co-morbidity

2011 ◽  
Vol 106 (11) ◽  
pp. 849-857 ◽  
Author(s):  
Nekeithia Wade ◽  
Amy Major
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Cardiovascular Disease ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Inflammatory Responses ◽  
Systemic Lupus ◽  
Accelerated Atherosclerosis ◽  
Increased Risk ◽  
Co Morbidity

SummaryRheumatic autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus (SLE), are associated with antibodies to “self” antigens. Persons with autoimmune diseases, most notably SLE, are at increased risk for developing accelerated cardiovascular disease. The link between immune and inflammatory responses in the pathogenesis of cardiovascular disease has been firmly established; yet, despite our increasing knowledge, accelerated atherosclerosis continues to be a significant co-morbidity and cause of mortality in SLE. Recent animal models have been generated in order to identify mechanism(s) behind SLE-accelerated atherosclerosis. In addition, clinical studies have been designed to examine potential treatments options. This review will highlight data from recent studies of immunity in SLE and atherosclerosis and discuss the potential implications of these investigations.

scholarly journals PADI4 Polymorphisms Confer Risk of Anti-CCP-Positive Rheumatoid Arthritis in Synergy With HLA-DRB1*04 and Smoking

2021 ◽  
Vol 12 ◽  
Author(s):  
Laura Massarenti ◽  
Christian Enevold ◽  
Dres Damgaard ◽  
Niels Ødum ◽  
Peter Garred ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Smoking Status ◽  
Nucleotide Polymorphisms ◽  
Regression Analyses ◽  
Post Translational Modification ◽  
Pathogenic Role ◽  
Single Nucleotide ◽  
Increased Risk ◽  
Citrullinated Protein ◽  
Reduced Risk

Peptidylarginine deiminases (PADs) catalyze citrullination, a post-translational modification playing a pathogenic role in anti-citrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA). The interplay between single nucleotide polymorphisms (SNPs) in the PADI genes and known risk factors for ACPA-positive RA, including smoking, HLA-DR4 and -1, and the PTPN22 R620W polymorphism, was investigated. We typed four PADI2 SNPs, four PADI4 SNPs, and the PTPN22 R620W SNP in 445 Danish RA patients and 533 age-matched healthy controls, as well as in 200 North American RA patients and 100 age- and sex-matched controls. The HLA-DRB1 locus was typed in the Danish cohort. Logistic regression analyses, adjusted for age, sex, smoking status, and PTPN22 R620W, revealed increased risk of anti-CCP-positive RA in carriers of rs11203367(T) (OR: 1.22, p=0.03) and reduced risk in carriers of rs2240335(A) in PADI4 (OR: 0.82, p=0.04). rs74058715(T) in PADI4 conferred reduced risk of anti-CCP-negative RA (OR: 0.38, p=0.003). In HLA-DRB1*04-positive individuals, specifically, the risk of anti-CCP-positive RA was increased by carriage of PADI4 rs1748033(T) (OR: 1.54, p=0.007) and decreased by carriage of PADI4 rs74058715(T) (OR: 0.44, p=0.01), and we observed an interaction between these SNPs and HLA-DRB1*04 (p=0.004 and p=0.008, respectively) Thus, PADI4 polymorphisms associate with ACPA-positive RA, particularly in HLA-DRB1*04-positive individuals, and with ACPA-negative RA independently of HLA-DRB1*04.

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