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1.
Clin Rheumatol ; 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34586516

RESUMO

This study aimed to evaluate the prevalence of, and the factors associated with, frailty in Japanese patients with rheumatoid arthritis (RA). Patients with RA enrolled in the Institute of Rheumatology Rheumatoid Arthritis (IORRA) cohort completed self-administered questionnaires, which included the 5-item frailty screening index. Patients were classified as frail, prefrail, or robust based on the 5 components of the frailty screening index. Logistic regression analyses were used to evaluate associations between clinical variables and frailty. Among 3,290 Japanese patients with RA (86.7% female, mean age 62.4 years) who participated this frailty study, 549 (16.7%) patients were categorized as frailty, 2,063 (62.7%) as prefrailty, and 678 (20.6%) as robust. In multivariable models, body mass index (BMI) ≥ 25 kg/m2 (odds ratio [OR] 1.87, 95% confidence interval [CI] 1.41 to 2.47), BMI < 18.5 kg/m2 (OR 1.31, 95% CI 1.00 to 1.71), disease activity scores in 28 joints (DAS28) (OR 1.32, 95% CI 1.18 to 1.47), Japanese version of Health Assessment Questionnaire disability index (J-HAQ) (OR 1.26, 95% CI 1.04 to 1.52), the European Quality of Life-5 Dimensions (EQ-5D) (OR 0.80, 95% CI 0.74 to 0.85), non-steroidal anti-inflammatory drug (NSAID) use (OR 1.59, 95% CI 1.23 to 1.98), and methotrexate (MTX) use (OR 0.75, 95% CI 0.60 to 0.94) were significantly (P < 0.05) associated with frailty. BMI (both overweight and underweight), DAS28, J-HAQ, EQ-5D, NSAID use, and MTX nonuse appear to be associated with frailty in Japanese patients with RA. Key Points • This is the largest study showing the prevalence and the associated factors of frailty in patients with RA. • Maintaining normal BMI appears to be important for preventing frailty in patients with RA. • We confirmed the significant associations of frailty with high disease activity, high degree of disability, and poor health related QOL in Japanese patients with RA. • NSAID use and MTX nonuse were associated with the frailty in Japanese patients with RA, which could be explained by patients' background.

2.
Arch Osteoporos ; 16(1): 119, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34342724

RESUMO

In this study, we assess the association between the occurrence of new fractures and vitamin D deficiency in Japanese patients with rheumatoid arthritis using our large IORRA cohort. The results suggest that vitamin D deficiency is a significant risk factor for new fractures in Japanese female patients over the age of 50 years with rheumatoid arthritis. PURPOSE: Both rheumatoid arthritis (RA) and menopause are known risk factors for the onset of osteoporosis. The occurrence of new clinical fractures in patients with RA can significantly lower quality of life. The purpose of this study was to investigate whether vitamin D deficiency in Japanese women with RA could be a risk factor for new fractures. METHODS: Between 2011 and 2017, a total of 2567 female patients with RA over the age of 50 years (mean age, 65.9 years) were enrolled in a prospective observational study. Self-reported occurrences of new fractures were verified using patient medical records. Vitamin D deficiency was defined as serum 25(OH)D levels < 20 ng/mL. Cox proportional hazards models were used to analyze the independent contributions of various risk factors to the occurrence of a new fracture. RESULTS: New clinical fractures were sustained by 205 patients in the included cases. Among them, new osteoporotic fractures were sustained by 139 patients (63 vertebral fractures and 76 non-vertebral fractures). Among all patients, the mean (SD) serum 25(OH)D level was 16.9 (5.89) ng/mL and the prevalence of vitamin D deficiency was 72.6%. A Cox proportional hazards model revealed that vitamin D deficiency was significantly associated with all new clinical fractures (hazard ratio, 1.44 [95% confidence interval 1.02‒2.05]; p = 0.0365) and all new osteoporotic fractures (hazard ratio, 1.75 [95% confidence interval 1.14‒2.69]; p = 0.0109). CONCLUSION: Vitamin D deficiency is a risk factor for new fractures in Japanese female patients over the age of 50 years with RA. Screening these patients for serum 25(OH)D could potentially be seminal to reducing their risk of fractures.


Assuntos
Artrite Reumatoide , Fraturas por Osteoporose , Deficiência de Vitamina D , Idoso , Artrite Reumatoide/epidemiologia , Estudos de Coortes , Feminino , Humanos , Japão/epidemiologia , Pessoa de Meia-Idade , Fraturas por Osteoporose/epidemiologia , Pós-Menopausa , Qualidade de Vida , Fatores de Risco , Vitamina D , Deficiência de Vitamina D/epidemiologia
6.
Osteoporos Sarcopenia ; 6(2): 82-87, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32715099

RESUMO

Objectives: This study aimed to evaluate factors associated with osteoporosis medication use in Japanese patients with rheumatoid arthritis (RA). Methods: Patients with RA who enrolled in our cohort completed self-administered questionnaires which included questions regarding their osteoporosis medications. Logistic regression was used to determine the association of variables with the use of these medications. Results: Among 5660 Japanese patients with RA who responded to the questionnaires (mean age, 61.8 years; 86.0% female), 1983 patients (35.0%) and 1211 patients (21.4%) reported taking osteoporosis medications and antiresorptive agents, respectively. In multivariate models, age, female sex, lower body mass index (BMI), self-reported fracture history, Japanese Health Assessment Questionnaire-Disability Index (JHAQ-DI), daily dosage of prednisone (PSL), weekly dosage of methotrexate (MTX), and concomitant use of hypertension and hyperlipidemia medications were significantly associated with the use of osteoporosis medications (P < 0.05). Among women with RA, the use of hypertension medications was significantly correlated with the use of both osteoporosis medications and antiresorptive agents (P < 0.05). Conclusions: Age, female sex, a lower BMI, duration of RA, self-reported fracture history, JHAQ-DI, daily dosage of PSL, weekly dosage of MTX, and the use of medications for hypertension and hyperlipidemia appear to be associated with the use of osteoporosis medications in Japanese patients with RA.

7.
Mod Rheumatol ; 30(3): 465-470, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31116056

RESUMO

Objectives: This study aimed to evaluate the prevalence of, and the factors associated with, periodontal disease in Japanese patients with rheumatoid arthritis (RA).Methods: Patients with RA enrolled in the Institute of Rheumatology Rheumatoid Arthritis (IORRA) cohort completed three self-administered questionnaires including questions about recent gingival bleeding during toothbrushing, a recent diagnosis of periodontitis by a dentist, and any history of periodontitis. Logistic regression analyses were used to evaluate associations with clinical variables for each questionnaire.Results: Among 5600 Japanese patients with RA, 31.0%, 18.3%, and 20.4% of patients self-reported recent gingival bleeding during toothbrushing, a recent diagnosis of periodontitis by a dentist, and a history of periodontitis, respectively. In multivariate models, younger age, fracture history, Japanese Health Assessment Questionnaire-Disability Index (JHAQ-DI), and prednisolone dosage were significantly (p < .05) associated with recent gingival bleeding during toothbrushing. Older age, female gender, and ever-smoker status were significantly correlated with a recent diagnosis of periodontitis.Conclusion: Many Japanese patients with RA experience gingival bleeding during toothbrushing and are diagnosed with periodontitis. Age, female gender, ever-smoker status, fracture history, JHAQ-DI, and prednisolone dosage appeared to be associated with periodontal disease in Japanese patients with RA.


Assuntos
Artrite Reumatoide/epidemiologia , Doenças Periodontais/epidemiologia , Fatores Etários , Idoso , Artrite Reumatoide/complicações , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Prevalência , Autorrelato , Fatores Sexuais
8.
Mod Rheumatol ; 30(1): 1-6, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31475852

RESUMO

Real-world evidence, based on real-world data from routine clinical treatment, is becoming increasingly important for providing high-quality medical care. Large-scale cohort studies can provide useful access to some of this real-world evidence, as shown by the IORRA (Institute of Rheumatology, Rheumatoid Arthritis) cohort in Japan. This large cohort study of patients with rheumatoid arthritis (RA) has been surveying enrolled participants since its inception in 2000. In the last 19 years, it has served as a database for a wide range of research in areas including transitions in medical care at the clinical level, changes in therapeutic drugs, approaches to comorbidities, developments in pharmacoeconomics, and the effects of genomic information on treatment options. This research has resulted in the publication of 133 articles in English to date. IORRA monitors changes in the management of RA, and has quantified over time the daily experience of clinicians who provide routine medical care. Such observational databases, which reflect the reality of daily clinical practice, will become increasingly important and may provide a model for similar research in other disease areas.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Reumatologia/métodos , Estudos de Coortes , Humanos , Japão , Estudos Observacionais como Assunto
9.
Mod Rheumatol ; 29(3): 430-435, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-29799293

RESUMO

OBJECTIVE: The aim of this study was to investigate factors that predict a decrease in serum 25(OH)D among Japanese patients with rheumatoid arthritis (RA). METHODS: In 2011 and 2013, serum 25(OH)D was evaluated in the same 2534 Japanese patients with RA (2179 women and 355 men) who participated in the Institute of Rheumatology Rheumatoid Arthritis (IORRA) cohort study. A vitamin D deficiency was defined as serum 25(OH)D levels <20 ng/mL. Predictive factors resulting in decreased serum 25(OH)D over a 2-year period were evaluated using multivariate logistic regression. RESULTS: The prevalence of vitamin D deficiency was 73.3% in 2011 and 68.2% in 2013. Serum 25(OH)D levels decreased by >5 ng/mL from 2011 to 2013 in 224 (8.8%) patients. A serum 25(OH)D decrease of >5 ng/mL was significantly associated with female gender, younger age, and disuse of bisphosphonates among all patients, and younger age, higher Japanese health assessment questionnaire disability index (JHAQ-DI), increased tender joint counts, and disuse of bisphosphonates and/or active vitamin D3 among women with RA. CONCLUSION: Female gender, younger age, JHAQ-DI, tender joint counts, and disuse of bisphosphonates and/or active vitamin D3 appear to be associated with a decrease in serum 25(OH)D in Japanese patients with RA.


Assuntos
Artrite Reumatoide/complicações , Deficiência de Vitamina D/epidemiologia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Vitamina D/sangue
10.
Clin Calcium ; 27(5): 691-698, 2017.
Artigo em Japonês | MEDLINE | ID: mdl-28439057

RESUMO

Female patients with rheumatoid arthritis(RA)are at high risk for osteoporosis and fractures. In Japanese female patients with RA, age, disability, daily prednisolone dose, history of total knee replacement, and low bone mineral density are known to be risk factors for fractures, and more than 70% are reported to be vitamin D deficiency.


Assuntos
Artrite Reumatoide/complicações , Densidade Óssea , Osteoporose/etiologia , Fraturas por Osteoporose/etiologia , Feminino , Humanos , Osteoporose/fisiopatologia , Fraturas por Osteoporose/fisiopatologia , Fatores de Risco , Vitamina D/sangue
11.
J Bone Miner Metab ; 35(3): 344-350, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27372662

RESUMO

This study aimed to evaluate dental treatments, tooth extractions, and osteonecrosis of the jaw (ONJ) in Japanese patients with rheumatoid arthritis (RA). Patients with RA enrolled in our cohort completed self-administered questionnaires, which included questions regarding their dental treatments, tooth extractions by dentists during the past 6 months, and past history of ONJ. The history of ONJ was validated with the patients' medical records. Logistic regression was used to determine the association of variables with dental treatments and tooth extractions during the past 6 months. Among 5695 Japanese patients with RA who responded to the questionnaires (mean age, 61.0 years; 85.6 % female), 2323 patients (40.8 %) and 378 patients (6.6 %) reported having had dental treatments and tooth extractions performed by a dentist within the past 6 months, respectively. In multivariate models, advanced age was significantly (P < 0.0001) associated with both dental treatments and tooth extractions during the prior 6-month period, and ever smoking was significantly (P = 0.023) correlated with tooth extractions during that time. Among patients who reported a history of ONJ, we confirmed five cases of ONJ with patient medical records. The prevalence of ONJ was 0.094 % among all RA patients and 0.26 % among female RA patients ≥65 years of age (n = 1888). Our data suggest that more than a few Japanese patients with RA have dental complications that require care by dentists, and that Japanese rheumatologists and dentists should cooperate to improve dental health in patients with RA.


Assuntos
Artrite Reumatoide/complicações , Grupo com Ancestrais do Continente Asiático , Doenças Maxilomandibulares/complicações , Osteonecrose/complicações , Extração Dentária , Estudos de Coortes , Feminino , Humanos , Doenças Maxilomandibulares/diagnóstico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Osteonecrose/diagnóstico , Inquéritos e Questionários
12.
J Bone Miner Metab ; 34(2): 201-8, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25794468

RESUMO

Minodronate is a potent nitrogen-containing bisphosphonate that can be administered according to a monthly (every 4 weeks) dosing regimen. A 6-month, cluster-randomized, open-label, multicenter, crossover trial was conducted to test the preference of Japanese patients with osteoporosis for monthly bisphosphonate versus weekly bisphosphonate. One hundred and forty-seven patients (postmenopausal women and men) with primary osteoporosis were recruited at eight outpatient clinics. The clinics were randomized into two groups according to the dosing protocol-monthly minodronate followed by weekly alendronate or risedronate for a total of 24 weeks, or weekly alendronate or risedronate followed by monthly minodronate for 24 weeks. Patient preference for either the monthly or weekly bisphosphonate regimen was evaluated using a preference questionnaire. One hundred and fifteen patients (78.2 %) who completed the trial were processed for the analyses. Significantly more patients preferred the monthly bisphosphonate regimen (65.2 %) than the weekly bisphosphonate regimen (15.7 %) (P = 0.007). 'Dosing schedule fits lifestyle better' was the most common reason given for the patient preference for both the monthly (32.0 %) and weekly bisphosphonate (33.3 %) regimens. Significantly more patients found the monthly bisphosphonate regimen to be more convenient (73.0 %) than the weekly bisphosphonate regimen (13.9 %) (P < 0.0001). The safety profiles of the two regimens were similar. The present trial demonstrated a strong patient preference for and the convenience of the monthly bisphosphonate regimen over the weekly bisphosphonate regimen in Japanese patients with osteoporosis.


Assuntos
Alendronato/uso terapêutico , Difosfonatos/administração & dosagem , Difosfonatos/uso terapêutico , Imidazóis/uso terapêutico , Osteoporose/tratamento farmacológico , Preferência do Paciente , Ácido Risedrônico/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Alendronato/administração & dosagem , Alendronato/efeitos adversos , Estudos Cross-Over , Demografia , Difosfonatos/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Imidazóis/administração & dosagem , Imidazóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ácido Risedrônico/administração & dosagem , Ácido Risedrônico/efeitos adversos
14.
Rheumatol Int ; 36(2): 213-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26420406

RESUMO

To our knowledge, no prior report focused on the risk factors for proximal humerus fractures in patients with rheumatoid arthritis. The purpose of this study was to evaluate the association between potential risk factors and the occurrence of proximal humerus fractures in patients with rheumatoid arthritis. A total of 11,907 patients with rheumatoid arthritis were enrolled in our observational cohort rheumatoid arthritis study between 2000 and 2012. Self-reported proximal humerus fractures were verified using the patients' medical records. Cox proportional hazard models were used to analyze the independent contribution of risk factors to the occurrence of proximal humerus fractures. During follow-up (mean 5.6 years), 92 proximal humerus fractures were verified in 91 patients. Multivariate Cox regression analyses estimated that the hazard ratios of sustaining a proximal humerus fracture were 1.37 for every 10-year increase in age [95 % confidence interval (CI) 1.10-1.70; P < 0.01], 1.95 for increases in serum C-reactive protein levels (mg/100 mL; 95 % CI 1.15-3.34; P < 0.05), 2.13 for a history of fractures (95 % CI 1.34-3.40; P < 0.01), 1.07 for the daily prednisolone dose (per mg; 95 % CI 1.01-1.13; P < 0.05), and 1.97 for oral bisphosphonate use (95 % CI 1.20-3.23; P < 0.01). Better control of rheumatoid arthritis with a smaller daily prednisolone dose in elderly patients with a history of fractures may be important for preventing proximal humerus fractures.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Conservadores da Densidade Óssea/administração & dosagem , Difosfonatos/administração & dosagem , Glucocorticoides/administração & dosagem , Prednisolona/administração & dosagem , Serviços Preventivos de Saúde , Fraturas do Ombro/prevenção & controle , Adulto , Fatores Etários , Idoso , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico , Biomarcadores/sangue , Proteína C-Reativa/análise , Feminino , Glucocorticoides/efeitos adversos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prednisolona/efeitos adversos , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fraturas do Ombro/diagnóstico , Fraturas do Ombro/etiologia , Fatores de Tempo
15.
Mod Rheumatol ; 25(3): 373-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25797805

RESUMO

OBJECTIVE: The aim of this study was to evaluate the associations between potential risk factors and the occurrence of established vertebral fractures in Japanese patients with rheumatoid arthritis (RA). METHODS: A total of 10,469 patients with RA were enrolled in a prospective, observational study from 2000 to 2011. Self-reported vertebral fractures were verified using patient's medical records and radiographs. Cox proportional hazards models were used to analyze independent contributions of various risk factors for established vertebral fracture occurrence. RESULTS: During a mean follow-up of 5.8 years, established vertebral fractures in 170 patients were verified with medical records and radiographs. Multivariate Cox regression analyses estimated that the hazards ratios of sustaining vertebral fractures increased by 1.84 for female gender, 1.72 for every 10 years of increased age, 1.26 for Disease Activity Score in 28 joints (DAS28), 1.44 for Japanese Health Assessment Questionnaire-Disability Index (J-HAQ-DI), 2.21 for history of any previous fractures, and 1.09 for daily prednisolone dose (mg/day). CONCLUSION: We confirmed the associations between vertebral fractures and advanced age, J-HAQ-DI, and high daily prednisolone dose; and found significant correlations between vertebral fractures and female gender, DAS28, and history of any previous fracture in Japanese RA patients.


Assuntos
Artrite Reumatoide/complicações , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia , Adulto , Fatores Etários , Idoso , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prednisolona/efeitos adversos , Prednisolona/uso terapêutico , Estudos Prospectivos , Radiografia , Fatores de Risco , Fatores Sexuais , Fraturas da Coluna Vertebral/diagnóstico por imagem
16.
J Bone Miner Metab ; 33(1): 55-60, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24442791

RESUMO

Prescription of a bisphosphonate (BP) with monthly dosing has recently been approved in Japan. The value of this approach for improvement of medication adherence was investigated in patients undergoing drug therapy for osteoporosis. A questionnaire was distributed to patients receiving treatment for osteoporosis at 8 medical facilities (5 orthopedic, 2 gynecology, and one internal medicine). Responses were collected from 1,300 patients. After exclusion of those who missed an item on the questionnaire or took drugs other than oral drugs, responses from 1,151 patients were analyzed. The most frequently used drug for treatment of osteoporosis was a once-weekly BP. Of the 1,151 patients, 38.4 % reported forgetting to take their current drug. The most frequent concern was 'I cannot feel an effect', but 73.2 % answered 'I have no concerns'. Regarding the most appropriate dosing regimen for long-term treatment, 60.3 % selected once-weekly and 24 % selected once every 4 weeks. Based on a recommendation by a physician of a drug to be taken monthly, 32.5 % wanted to switch, 31.8 % were undecided, and 35.7 % wanted to continue with their current drug. The desire for a change was higher among patients currently taking a once-weekly BP (52.3 %) than among patients taking a daily BP (29.5 %) or a SERM (19.4 %). This survey revealed patients' preferences in osteoporosis drug therapy. It is important to select a drug for osteoporosis based on the efficacy and the drug regimen preferred by the individual patient.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Difosfonatos/administração & dosagem , Adesão à Medicação , Osteoporose/tratamento farmacológico , Idoso , Conservadores da Densidade Óssea/química , Difosfonatos/química , Esquema de Medicação , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
17.
PLoS One ; 9(8): e104587, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25105978

RESUMO

INTRODUCTION: Patients with rheumatoid arthritis (RA) have a higher prevalence of osteoporosis and hip fracture than healthy individuals. Multiple genetic loci for osteoporotic fracture were identified in recent genome-wide association studies. The purpose of this study was to identify genetic variants associated with the occurrence of hip fracture in Japanese patients with RA. METHODS: DNA samples from 2,282 Japanese patients with RA were obtained from the DNA collection of the Institute of Rheumatology Rheumatoid Arthritis cohort (IORRA) study. Six single nucleotide polymorphisms (SNPs) that have been reported to be associated with fractures in recent studies were selected and genotyped. Forty hip fractures were identified with a maximum follow-up of 10 years. The genetic risk for hip fracture was examined using a multivariate Cox proportional hazards regression model. RESULTS: The risk analyses revealed that patients who are homozygous for the major allele of SNP rs6993813, in the OPG locus, have a higher risk for hip fracture (hazard ratio [95% CI] = 2.53 [1.29-4.95], P = 0.0067). No association was found for the other SNPs. CONCLUSIONS: Our results indicate that an OPG allele is associated with increased risk for hip fracture in Japanese patients with RA.


Assuntos
Artrite Reumatoide/complicações , Fraturas do Quadril/complicações , Fraturas do Quadril/genética , Osteoprotegerina/genética , Polimorfismo de Nucleotídeo Único , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Coortes , Feminino , Estudo de Associação Genômica Ampla , Fraturas do Quadril/epidemiologia , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Risco
18.
Clin Calcium ; 24(5): 743-9, 2014 May.
Artigo em Japonês | MEDLINE | ID: mdl-24769686

RESUMO

Patients with rheumatoid arthritis (RA) are at increased risk for developing osteoporosis and fractures compared to controls. This risk is further increased since a majority of patients with RA also receive concomitant corticosteroids, which have been shown to induce osteoporosis and increase the risk of fractures. Glucocorticoids use and physical disability as well as low bone mineral density and older age are recognized as significant risk factors for fractures in patients with RA. This article reviews the epidemiology and treatment for osteoporosis in Japanese patients with RA.


Assuntos
Acidentes por Quedas/estatística & dados numéricos , Artrite Reumatoide/terapia , Osteoporose/terapia , Fraturas por Osteoporose/terapia , Artrite Reumatoide/complicações , Grupo com Ancestrais do Continente Asiático , Humanos , Osteoporose/complicações , Osteoporose/diagnóstico , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Fatores de Risco
19.
PLoS One ; 9(3): e90019, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24632671

RESUMO

BACKGROUND: Accumulating evidence has shown that several non-HLA genes are involved in the susceptibility to polymyositis/dermatomyositis. This study aimed to investigate the involvement of C8orf13-BLK, one of the strongest candidate genes for autoimmune diseases, in susceptibility to polymyositis/dermatomyositis in the Japanese population. A possible gene-gene interaction between C8orf13-BLK and STAT4, which we recently showed to be associated with Japanese polymyositis/dermatomyositis, was also analyzed. METHODS: A single-nucleotide polymorphism in C8orf13-BLK (dbSNP ID: rs13277113) was investigated in the Japanese population using a TaqMan assay in 283 polymyositis patients, 194 dermatomyositis patients, and 656 control subjects. RESULTS: The C8orf13-BLK rs13277113A allele was associated with overall polymyositis/dermatomyositis (P<0.001, odds ratio [OR] 1.44, 95% confidence interval [CI] 1.19-1.73), as well as polymyositis (P = 0.011, OR 1.32, 95% CI 1.06-1.64) and dermatomyositis (P<0.001, OR 1.64, 95% CI 1.26-2.12). No association was observed between the C8orf13-BLK rs13277113A allele and either interstitial lung disease or anti-Jo-1 antibody positivity. The C8orf13-BLK rs13277113 A and STAT4 rs7574865 T alleles had an additive effect on polymyositis/dermatomyositis susceptibility. The strongest association was observed in dermatomyositis, with an OR of 3.07 (95% CI; 1.57-6.02) for the carriers of four risk alleles at the two SNP sites, namely, rs1327713 and rs7574865. CONCLUSIONS: This study established C8orf13-BLK as a new genetic susceptibility factor for polymyositis/dermatomyositis. Both C8orf13-BLK and STAT4 exert additive effects on disease susceptibility. These observations suggested that C8orf13-BLK, in combination with STAT4, plays a pivotal role in creating genetic susceptibility to polymyositis/dermatomyositis in Japanese individuals.


Assuntos
Dermatomiosite/genética , Polimiosite/genética , Proteínas/genética , Fator de Transcrição STAT4/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Feminino , Predisposição Genética para Doença/genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Proteínas/metabolismo , Fator de Transcrição STAT4/metabolismo
20.
Arthritis Res Ther ; 16(2): R75, 2014 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-24646907

RESUMO

INTRODUCTION: Vitamin D deficiency has been reported to be common in patients with rheumatoid arthritis (RA) who have a higher prevalence of osteoporosis and hip fracture than healthy individuals. Genetic variants affecting serum 25-hydroxyvitamin D (25(OH)D) concentration, an indicator of vitamin D status, were recently identified by genome-wide association studies of Caucasian populations. The purpose of this study was to validate the association and to test whether the serum 25(OH)D-linked genetic variants were associated with the occurrence of hip fracture in Japanese RA patients. METHODS: DNA samples of 1,957 Japanese RA patients were obtained from the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort DNA collection. First, five single nucleotide polymorphisms (SNPs) that were reported to be associated with serum 25(OH)D concentration by genome-wide association studies were genotyped. The SNPs that showed a significant association with serum 25(OH)D level in the cross-sectional study were used in the longitudinal analysis of hip fracture risk. The genetic risk for hip fracture was determined by a multivariate Cox proportional hazards model in 1,957 patients with a maximum follow-up of 10 years (median, 8 years). RESULTS: Multivariate linear regression analyses showed that rs2282679 in GC (the gene encoding group-specific component (vitamin D binding protein)) locus was significantly associated with lower serum 25(OH)D concentration (P = 8.1 × 10⁻5). A Cox proportional hazards model indicated that rs2282679 in GC was significantly associated with the occurrence of hip fracture in a recessive model (hazard ratio (95% confidence interval) = 2.52 (1.05-6.05), P = 0.039). CONCLUSIONS: A two-staged analysis demonstrated that rs2282679 in GC was associated with serum 25(OH)D concentration and could be a risk factor for hip fracture in Japanese RA patients.


Assuntos
Artrite Reumatoide/complicações , Artrite Reumatoide/genética , Predisposição Genética para Doença/genética , Fraturas do Quadril/genética , Polimorfismo de Nucleotídeo Único , Proteína de Ligação a Vitamina D/genética , Vitamina D/análogos & derivados , Idoso , Artrite Reumatoide/sangue , Grupo com Ancestrais do Continente Asiático , Estudos de Coortes , Estudos Transversais , Feminino , Seguimentos , Genótipo , Fraturas do Quadril/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Vitamina D/sangue , Vitamina D/genética
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