Rheumatoid Arthritis In Women Research Articles

Association Between Composite Dietary Antioxidant Index and the Risk of Endometriosis-Related Rheumatoid Arthritis in Women of Childbearing Age: A Cross-Sectional Study Based on the National Health and Nutrition Examination Survey Database.

To evaluate the association between Composite Dietary Antioxidant Index (CDAI) and the risk of endometriosis (EM)-related rheumatoid arthritis (RA) in women of childbearing age. Using the data from the National Health and Nutrition Examination Survey database, this cross-sectional study included women of childbearing age. The CDAI was obtained by summing the standardized Z-values of the dietary intakes. EM was diagnosed based on a questionnaire-based survey. The outcome of this study was the presence of RA, which was defined by a questionnaire. The associations of CDAI and EM with the risk of RA were determined using weighted logistic analysis. Additive interaction was evaluated using the relative excess risk due to interaction (RERI), the attributable proportion due to interaction (AP), and the synergy index (S). In total, 3803 patients were included, of which 74 patients (1.99%) were with RA. A lower CDAI [odds ratio (OR): 1.85, 95% confidence interval (CI): 1.12 to 3.04, P= 0.015] and the presence of EM (OR: 3.05, 95% CI: 1.19 to 7.81, P= 0.023) was associated with the risk of RA. The result demonstrated an additive interaction of a lower CDAI and the presence of EM on the risk of RA (OR: 6.19, 95% CI: 2.33 to 16.43, P <0.001, P of trend =0.007). Nevertheless, there was no significant additive interaction after being assessed by the RERI, AP, and S. However, a joint effect of a lower CDAI and EM on the risk of RA (OR: 3.94, 95% CI: 1.35 to 11.51, P= 0.013) was observed. Our study identified EM, and lower CDAI, was related to the risk of RA. Lower CDAI score was also associated with the risk of EM-related RA. This study indicates the importance of antioxidant intake in daily diet for the management of EM-related RA.

Update on hydroxychloroquine use in pregnancy.

It is well-known that hydroxychloroquine (HCQ) treats malaria, systemic lupus erythematosus, and rheumatoid arthritis in women for its immunomodulatory and anti-inflammatory action. Additionally, HCQ was used in cases with refractory antiphospholipid syndrome. HCQ safety was reinforced in pregnant women owing to insignificant reports of adverse pregnancy outcomes and major congenital malformation. Recently, HCQ was tested in cases with chronic placental inflammation with a promising result of increased life birth; however, its benefit needs further validation. We aimed to highlight the recent updates for HCQ use in various conditions in pregnancy.

Artificially Sweetened Beverages Beyond the Metabolic Risks: A Systematic Review of the Literature.

We carried out a review of the available literature on the effects that artificially sweetened beverages (ASBs) such as diet soda (DS)have on health, particularly those not related to incident diabetes mellitus, obesity, and metabolic syndrome. A search of scientific articles was carried out using 11 different databases: PubMed, Cochrane, LILACS, MEDLINE Ovid, JAMA Network, IBECS, Cumed, Scopus, SciELO, MEDLINE-EBSCO, and Taylor & Francis Online. Articles published in the last 10 years were considered, considering cross-sectional studies, retrospective or prospective cohort studies, case-control studies, and randomized controlled clinical trials. Only articles in Spanish or English were considered using the MeSH (Medical Subject Heading) and DeCS (Descriptores en Ciencias de la Salud) terms, including "Diet soda," "Health," "Artificial sweetener," "Gaseosa sin azúcar," "Refresco sin azúcar," and "Salud." Additionally, Boolean operators "AND" and "Y" were used. A total of 1,323 articles were obtained in the initial search, of which 21 main ones were selected for review, which included the topic of DS consumptionand explored the health consequences that it poses on different organs. The question of whetherASBssuch as DSare a preferred substitute is becoming more and more important in terms of public policy due to mounting evidence of the potential negative health effects of their excessive consumption. This systematic review, the first of its kind to our knowledge, sheds light on how excessive DS consumption can affect multiple organ systems, and associations have been made to mental health burden, delays in child neurodevelopment, cardiac remodeling, worsening retinopathy in diabetics, incidental end-stage renal disease, non-Hodgkin's lymphoma and multiple myeloma in men, rheumatoid arthritis in women, hip fractures, dental erosion, increases in breath alcohol concentration when used in alcoholic beverages, and accelerated cell aging. Further studies should delve further to understand the pathophysiologic mechanisms of these associations.

Passive smoking in childhood and adulthood and risk of rheumatoid arthritis in women: results from the French E3N cohort study

ObjectiveThe association between passive smoking exposure in childhood or in adulthood, and the risk of rheumatoid arthritis (RA) has been incompletely investigated. We aimed to assess the relationship between exposure...

Діагностична роль остеосцинтиграфії у хворих на ревматоїдний артрит при ендопротезуванні кульшових суглобів

Актуальність. Ревматоїдний артрит є одним з найбільш поширених хронічних запальних захворювань суглобів. Поширеність захворювання серед дорослого населення у різних країнах світу становить від 0,6 до 5 %. Хворіють частіше люди працездатного віку. Пік захворювання припадає на 40–50 років, при цьому жінки хворіють у 2–4 рази частіше, ніж чоловіки. Захворюваність на ревматоїдний артрит у жінок збільшується після 30 років, досягаючи найбільших показників у 45–75 років. Мета: визначити діагностичну роль остеосцинтиграфії у хворих на ревматоїдний артрит при ендопротезуванні кульшових суглобів. Матеріали і методи. Остеосцинтиграфію проводили на томографічній сцинтиляційній однодетектерній гамма-камері «Тамара-301 Т» після внутрішньовенного введення 99m-Tc-пірофосфату активністю 550–770 МБк. Результати. Усіх хворих розподілили на три діагностичні групи. До першої групи було включено 34 (45 %) пацієнтів, у яких відсоток накопичення радіофармпрепарату в проекції ураженого суглоба дорівнював +10–80 %, до другої — 27 (36 %) хворих, у яких відсоток накопичення індикатору в проекції ураженого суглобового комплексу становив +81–150 %, третя група нараховувала 13 (19 %) пацієнтів із накопиченням індикатору в проекції ураженого суглобового комплексу більше ніж +150 %. Через 1 рік після ендопротезування ураженого кульшового суглоба у хворих першої діагностичної групи післяопераційних ускладнень не зафіксовано. У 3 (11 %) пацієнтів другої діагностичної групи та 19 (30 %) пацієнтів третьої діагностичної групи через рік після ендопротезування розвинулось імплант-асоційоване інфекційне ускладнення. ­Висновки. Чим вище відсоток включення радіофармпрепарату в проекції ураженого ревматоїдним артритом суглобового комплексу при остеосцинтиграфії в доопераційний період, тим вище вірогідність виникнення післяопераційних імплант-асоційованих ускладнень після ендопротезування (p &lt; 0,05).

Impact of VSIG4 gene polymorphisms on susceptibility and functional status of rheumatoid arthritis.

The complement receptor of the immunoglobulin superfamily (CRIg, encoded by the VSIG4 gene) is a macrophage receptor involved in the clearance of immune complexes and autologous cells. Our results suggest that the VSIG4 rs1044165T allele is a risk factor for severe functional status of rheumatoid arthritis in women, possibly by affecting VSIG4 gene expression.

Computer-aided diagnosis based on hand thermal, RGB images, and grip force using artificial intelligence as screening tool for rheumatoid arthritis in women.

Rheumatoid arthritis (RA) is an autoimmune disorder that typically affects people between 23 and 60years old causing chronic synovial inflammation, symmetrical polyarthritis, destruction of large and small joints, and chronic disability. Clinical diagnosis of RA is stablished by current ACR-EULAR criteria, and it is crucial for starting conventional therapy in order to minimize damage progression. The 2010 ACR-EULAR criteria include the presence of swollen joints, elevated levels of rheumatoid factor or anti-citrullinated protein antibodies (ACPA), elevated acute phase reactant, and duration of symptoms. In this paper, a computer-aided system for helping in the RA diagnosis, based on quantitative and easy-to-acquire variables, is presented. The participants in this study were all female, grouped into two classes: class I, patients diagnosed with RA (n = 100), and class II corresponding to controls without RA (n = 100). The novel approach is constituted by the acquisition of thermal and RGB images, recording their hand grip strength or gripping force. The weight, height, and age were also obtained from all participants. The color layout descriptors (CLD) were obtained from each image for having a compact representation. After, a wrapper forward selection method in a range of classification algorithms included in WEKA was performed. In the feature selection process, variables such as hand images, grip force, and age were found relevant, whereas weight and height did not provide important information to the classification. Our system obtains an AUC ROC curve greater than 0.94 for both thermal and RGB images using the RandomForest classifier. Thirty-eight subjects were considered for an external test in order to evaluate and validate the model implementation. In this test, an accuracy of 94.7% was obtained using RGB images; the confusion matrix revealed our system provides a correct diagnosis for all participants and failed in only two of them (5.3%). Graphical abstract.

A comparison of risk factors for osteo- and rheumatoid arthritis using NHANES data.

Osteoarthritis and rheumatoid arthritis are both diseases of joints, but they have very different etiologies. Osteoarthritis is a disease assumed to result from wear and tear over time, whereas rheumatoid arthritis is an autoimmune disease where the body's immune system attacks joint tissues. Using NHANES data (1999-2015), we have compared the influence of age, sex, ethnicity, body mass index and smoking on these two very different forms of arthritis. Incidence of both increases with age and are more frequent in females than males. There is little apparent difference between osteoarthritis and rheumatoid arthritis in women of normal as comparted to overweight, but both are more frequent in obese women, especially those over the age of 60. While osteoarthritis is more frequent in whites, blacks have more rheumatoid arthritis, and Hispanics show an intermediate prevalence. Smoking significantly increased the incidence of both osteoarthritis and rheumatoid arthritis in women, but increased prevalence of only RA in men. There was no effect of smoking on OA prevalence in males. It is remarkable that two diseases of joints, which have quite different causes, should have so many commonalities. The differences that exist appear to be due to a combination of inflammatory markers and access to health care.

Abdominal Obesity in Comparison with General Obesity and Risk of Developing Rheumatoid Arthritis in Women.

Being overweight or obese increases rheumatoid arthritis (RA) risk among women, particularly among those diagnosed at a younger age. Abdominal obesity may contribute to systemic inflammation more than general obesity; thus, we investigated whether abdominal obesity, compared to general obesity, predicted RA risk in 2 prospective cohorts: the Nurses' Health Study (NHS) and NHS II. We followed 50,682 women (1986-2014) in NHS and 47,597 women (1993-2015) in NHS II, without RA at baseline. Waist circumference (WC), BMI, health outcomes, and covariate data were collected through biennial questionnaires. Incident RA cases and serologic status were identified by chart review. We examined the associations of WC and BMI with RA risk using time-varying Cox proportional hazards models. We repeated analyses restricted to age ≤ 55 years. During 28 years of follow-up, we identified 844 incident RA cases (527 NHS, 317 NHS II). Women with WC > 88 cm (35 in) had increased RA risk (HR 1.22, 95% CI 1.06-1.41). A similar association was observed for seropositive RA, which was stronger among young and middle-aged women. Further adjustment for BMI attenuated the association to null. In contrast, BMI was associated with RA (HRBMI ≥ 30 vs < 25 1.33, 95% CI 1.05-1.68) and seropositive RA, even after adjusting for WC, and, as in WC analyses, this association was stronger among young and middle-aged women. Abdominal obesity was associated with increased RA risk, particularly for seropositive RA, among young and middle-aged women; however, it did not independently contribute to RA risk beyond general obesity.

Regular use of proton pump inhibitor and risk of rheumatoid arthritis in women: a prospective cohort study.

Proton pump inhibitors (PPIs) have a significant impact on the gut microbiome, which in turn, might increase the risk of rheumatoid arthritis (RA). To evaluate regular use of PPIs and risk of RA. This is a prospective analysis of the US nurses who reported PPI use data, and were free of RA from the Nurses' Health Study (NHS 2002-2014) and NHS II (2003-2015). The exposure was regular use of PPI in the past 2years, which was repeatedly evaluated in biennial surveys. RA was confirmed by the 1987 or 2010 American College of Rheumatology criteria. We estimated the hazard ratios (HRs) and confidence interval (CIs) with time-dependent Cox regression adjusting for potential confounders. We documented 421 cases of RA over 1753879 person-years of follow-up. Regular PPI users had a 44% higher risk of RA as compared with non-regular users (adjusted HR=1.44; 95%CI, 1.10-1.89). The risk of RA increased with the total duration of PPI use (P-trend=0.008). Compared with non-regular users, the adjusted HRs were 1.22 (95%CI, 0.93-1.62) for women with >0 to 4 years' use and 1.73 (95% CI, 1.14 to 2.61) for >4years' use. Regular use of PPI was associated with increased risk of RA in women, with a higher risk observed in individuals with a longer duration of PPI use. Due to the observational study design, large prospective trials are still required to confirm our finding.

Inflammatory dietary pattern and risk of developing rheumatoid arthritis in women

Our objective was to investigate whether a dietary pattern derived using inflammatory biomarkers is associated with rheumatoid arthritis (RA) risk. We prospectively followed 79,988 women in the Nurses' Health Study (NHS, 1984-2014) and 93,572 women in the NHSII (1991-2013); incident RA was confirmed by medical records. Food frequency questionnaires (FFQ) were completed at baseline and approximately every 4years. Inflammatory dietary pattern was assessed from FFQ data using the Empirical Dietary Inflammatory Pattern (EDIP), including 18 anti-/pro-inflammatory food/beverage groups weighted by correlations with plasma inflammatory biomarkers (interleukin-6, C-reactive protein, and tumor necrosis factor-α receptor 2). We investigated associations between EDIP and RA using Cox regression. We identified 1185 incident RA cases over 4,425,434 person-years. EDIP was not associated with overall RA risk (p trend = 0.21 across EDIP quartiles). Among women ≤ 55years, increasing EDIP was associated with increased overall RA risk; HRs (95% CIs) across EDIP quartiles were 1.00 (reference), 1.14 (0.86-1.51), 1.35 (1.03-1.77), and 1.38 (1.05-1.83; p for trend = 0.01). Adjusting for BMI attenuated this association. Increasing EDIP was associated with increased seropositive RA risk among women ≤ 55years (p for trend = 0.04). There was no association between EDIP and RA among women > 55years (EDIP-age interaction, p= 0.03). An inflammatory dietary pattern was associated with increased seropositive RA risk with onset ≤ 55years old, and this association may be partially mediated through BMI.

Influence of aromatase inhibitors therapy on the occurrence of rheumatoid arthritis in women with breast cancer: results from a large population-based study of the Italian Society for Rheumatology

ObjectivesThe purpose of this study was to evaluate the risk of developing rheumatoid arthritis (RA) in a population of patients with breast cancer treated with aromatase inhibitors (AIs) compared with...

Childhood Residential and Agricultural Pesticide Exposures in Relation to Adult-Onset Rheumatoid Arthritis in Women.

Farming and pesticide exposure may influence risk of rheumatoid arthritis (RA); the role of early-life pesticide exposure is unknown. The Sister Study includes a US national cohort of women aged 35-74 years (enrolled 2004-2009); we examined childhood pesticide exposure in women in this cohort with adult-onset RA. Cases (n = 424) were compared with 48,919 noncases. Data included pesticide use at the longest childhood residence through age 14 years, farm residence of at least 12 months with agricultural pesticide exposure through age 18 years, and maternal farm experience. Odds ratios and 95% confidence intervals were adjusted for age, race or ethnicity, education, smoking, and childhood socioeconomic factors. Cases with RA reported more frequent and direct (personal) residential pesticide use in childhood (for infrequent/indirect pesticide use, odds ratio (OR) = 1.1; for frequent/direct use, OR = 1.8; P for trend = 0.013). Compared with women without residential farm history, odds of having RA increased for those reporting a childhood-only farm residence with personal exposure to pesticides used on crops (OR = 1.8, 95% confidence interval: 1.1, 2.9) or livestock (OR = 2.0, 95% confidence interval: 1.2, 3.3). Our findings suggest adult-onset RA may be related to childhood exposure to residential and agricultural pesticides, and support further investigations of lifetime pesticide use in RA.

Long-term consumption of caffeine-free high sucrose cola beverages aggravates the pathogenesis of EAE in mice

Epidemiological data provide strong evidence of dramatically increasing incidences of many autoimmune diseases in the past few decades, mainly in western and westernized countries. Recent studies clearly revealed that ‘Western diet’ increases the risk of autoimmune diseases at least partially via disrupting intestinal tight junctions and altering the construction and metabolites of microbiota. However, the role of high sucrose cola beverages (HSCBs), which are one of the main sources of added sugar in the western diet, is barely known. Recently, a population study showed that regular consumption of sugar-sweetened beverages is associated with increased risk of seropositive rheumatoid arthritis in women, which provokes interest in the genuine effects of these beverages on the pathogenesis of autoimmune diseases and the underlying mechanisms. Here we showed that long-term consumption of caffeine-free HSCBs aggravated the pathogenesis of experimental autoimmune encephalomyelitis in mice in a microbiota-dependent manner. Further investigation revealed that HSCBs altered community structure of microbiota and increased Th17 cells. High sucrose consumption had similar detrimental effects while caffeine contamination limited the infiltrated pathogenic immune cells and counteracted these effects. These results uncovered a deleterious role of decaffeinated HSCBs in aggravating the pathogenesis of experimental autoimmune encephalomyelitis in mice.

Number of parity and the risk of rheumatoid arthritis in women: A dose-response meta-analysis of observational studies.

The association between parity and rheumatoid arthritis (RA) risk has been investigated, but results are controversial. Thus, our aim was to systematically analyze the effect of number of parity on the risk of RA in women. Relevant published studies were identified using PubMed and embase databases through 1 April 2016. We pooled the relative risks (RR) and 95% confidence intervals (CI) using random-effects models. In all, 12 studies with a total of 2 497 580 participants and 11 521 RA cases were included. A borderline significant inverse association was observed when we compared parity with nulliparity for RA, with summarized RR=0.90 (95%CI: 0.79-1.02; I2 =58.5%, Pheterogeneity =0.010). In dose-response analysis, we observed a significant nonlinear (Pnonlinearity =0.000) relation between parity number and the risk of RA. Compared with null parity, the pooled RR of RA were 0.89 (95%CI: 0.86-0.93), 0.84 (95%CI: 0.79-0.89), 0.85 (95%CI: 0.79-0.90), 0.88 (95%CI: 0.81-0.95), 0.90 (95%CI: 0.83-0.97), 0.92 (95%CI: 0.84-1.02), and 0.94 (95%CI: 0.83-1.07) for 1, 2, 3, 4, 5, 6, and 7 live births, respectively. Subgroup and sensitivity analyses showed similar associations. No publication bias was found. The findings from the current meta-analysis indicate that parity was related to decreased risk of RA. The greatest risk reduction appeared when the parity number reached two. Further studies are warranted to confirm our findings.

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...

A Prospective Study Investigating Prediagnostic Leukocyte Telomere Length and Risk of Developing Rheumatoid Arthritis in Women.

To prospectively examine the association between leukocyte telomere length (LTL) and subsequent rheumatoid arthritis (RA) development in women. Using a case-control design nested within the prospective Nurses' Health Study (NHS), NHS II (NHSII), and Women's Health Study (WHS), each validated case of RA with a prediagnostic blood sample was matched to 3 controls by cohort, age, menopausal status, postmenopausal hormone therapy, and blood collection covariates. We measured telomere length in genomic DNA extracted from stored buffy coat samples using quantitative PCR. We used unconditional logistic regression to determine OR and 95% CI, and random-effects metaanalysis to combine study results. In total, we analyzed 296 incident RA cases and 827 matched controls. Mean age of diagnosis among women who developed RA was 60.5 in NHS/NHSII and 61.3 in WHS. Metaanalysis demonstrated that longer prediagnostic LTL was associated with increased RA risk when women in the longest versus shortest LTL tertile were compared (OR 1.51, 95% CI 1.03-2.23, Pheterogeneity = 0.27). However, statistically significant between-study heterogeneity was observed for the intermediate tertile category (Pheterogeneity = 0.008). We did not observe heterogeneity by menopausal status, inflammatory cytokine levels, age at diagnosis, age at blood collection, body mass index, seropositivity, or HLA-DRβ1 shared epitope status. Our results do not support an involvement for short LTL preceding RA development.

High serum cholesterol predicts rheumatoid arthritis in women, but not in men: a prospective study.

IntroductionEnvironmental exposures, including smoking, hormone-related factors, and metabolic factors, have been implicated in the etiology of rheumatoid arthritis (RA). A previous study has indicated that blood lipid levels may influence the development of RA. The objective of this study was to investigate the impact of serum total cholesterol and triglycerides on the risk of RA in a prospective study.MethodsAmong participants in a large population-based health survey (n = 33,346), individuals who subsequently developed RA were identified by linkage to four different registers and a structured review of the medical records. In a nested case-control study, with controls, matched for age, sex, and year of inclusion, from the health survey database, the relation between serum lipids (levels of total cholesterol and triglycerides) and future RA development was examined.ResultsIn total, 290 individuals (151 men and 139 women) whose RA was diagnosed a median of 12 years (range of 1–28) after inclusion in the health survey were compared with 1160 controls. Women with a diagnosis of RA during the follow-up had higher total cholesterol levels at baseline compared with controls: odds ratio (OR) 1.54 per standard deviation; 95 % confidence interval (CI) 1.22–1.94. This association remained statistically significant in multivariate models adjusted for smoking and a history of early menopause and in analyses stratified by rheumatoid factor status and time to RA diagnosis. Total cholesterol had no significant impact on the risk of RA in men (OR 1.03; 95 % CI 0.83–1.26). Triglycerides did not predict RA in men or women.ConclusionsA high total cholesterol was a risk factor for RA in women but not in men. This suggests that sex-specific exposures modify the impact of lipids on the risk of RA. Hormone-related metabolic pathways may contribute to RA development.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0804-1) contains supplementary material, which is available to authorized users.

Mediterranean diet and incidence of rheumatoid arthritis in women.

We examined the association between a Mediterranean dietary pattern, as measured by the Alternate Mediterranean Diet Score (aMed), and risk of incident rheumatoid arthritis (RA) in US women. We prospectively followed 83,245 participants from the Nurses' Health Study (NHS; 1980-2008) and 91,393 participants from NHS II (1991-2009) who were initially free of baseline connective tissue diseases. Dietary information was obtained via validated food frequency questionnaires at baseline and approximately every 4 years during followup. The aMed score was calculated according to the consumption status of 9 food components using cumulative average value. Time-varying Cox proportional hazards models were used to calculate hazard ratios (HRs) for RA, seropositive RA, and seronegative RA after adjustment for potential confounding factors. Results from 2 cohorts were pooled by an inverse variance-weighted, fixed-effects model. During 3,511,050 person-years of followup, 913 incident cases of RA were documented in the 2 cohorts. After adjustment for several lifestyle and dietary variables, in both cohorts greater adherence to Mediterranean dietary pattern was not significantly associated with altered risk of RA. The pooled HR for women in the highest quartile of the aMed score was 0.98 (95% confidence interval 0.80-1.20) compared with those in the bottom quartile. Similar nonsignificant results were observed for both seropositive and seronegative RA. We did not find significant associations between each individual food component (except for alcohol) of the aMed score and risk of incident RA. We did not find a significant association between a Mediterranean dietary pattern and the risk of RA in women.

CYB5A polymorphism increases androgens and reduces risk of rheumatoid arthritis in women.

IntroductionRheumatoid arthritis (RA) is characterized by decreased androgen levels, which was the first hormonal abnormality described. Several studies indicated that steroidogenesis is directed towards endogenous glucocorticoids at the expense of androgens. The decisive step governing androgen synthesis is the 17,20-lyase activity of the CYP17A1 gene-encoded enzyme cytochrome P450 17A1. Here, we focused on the role in RA of the critical cofactor for 17,20-lyase activity, cytochrome b5, encoded by the CYB5A gene.MethodsData sets of two genome wide RA association studies (GWAS) were screened for single nucleotide polymorphisms (SNP) in the CYB5A gene. Candidate SNPs in CYB5A were studied in a case–control study population of Slovakia. Expression analyses were done in synovial fibroblasts from RA patients by quantitative real-time polymerase chain reaction, and cytochrome b5–expression was detected by immunohistochemistry. Real-life androgen production after steroid conversion was measured using radiolabeled substrates.ResultsThe study identified the RA-associated intronic SNP rs1790834 in the CYB5A gene in one GWAS and confirmed the same SNP in our study. The minor allele reduced RA risk selectively in women (P = 4.1*10−3; OR = 0.63, 95% CI [0.46-0.86]). The protective effect was confined to rheumatoid factor-positive (OR = 0.53, [0.37-0.75]) and anti-cyclic citrullinated peptide-positive (OR = 0.58, [0.41-0.83]) cases, respectively. The protective allele doubles CYB5A mRNA-expression resulting in 2-3fold activation of steroid 17,20-lyase activity, and protective allele was accompanied by a higher density of cytochrome b5-positive cells in synovial tissue.ConclusionsCYB5A is the first RA susceptibility gene involved in androgen synthesis. Our functional analysis of SNP rs1790834 indicates that it contributes to the sex bias observed in RA.