RESUMEN
Malaysia is a developing country in the South-East Asian region with a significant burden of disability from musculoskeletal disease. Rheumatology in Malaysia is a relatively young speciality. Currently, there is approximately 1 rheumatologist per 390,000 population, mostly concentrated in the urban areas. This article aims to give a brief overview of the research in rheumatology, the healthcare system, and rheumatology training and education in Malaysia. From 1950 until mid-2019, there were 547 publications about rheumatological conditions from Malaysia, with a 27-fold increase in the numbers from the period before 1980 compared to 2010-2019. Although there is universal access to healthcare through the public (government funded) hospitals and clinics, as well as a system of private healthcare, funding for expensive biological therapies remain patchy and scarce, leading to significant under-utilization of such treatments in rheumatology patients. Training in rheumatology in Malaysia is well established with a formalised training curriculum introduced in 2004, followed by the introduction of training in musculoskeletal ultrasound in 2006. To improve care for patients with musculoskeletal conditions, there has been regular continuing educational meetings and courses, not just for rheumatologists, but also for other medical professionals, as not all areas in Malaysia have easy access to rheumatology services. Thus overall, despite the small number of rheumatologists, rheumatology in Malaysia has made encouraging progress over the past 2 decades, but improvements in patient care, training, education and research need to continue in the future.
Asunto(s)
Enfermedades Musculoesqueléticas , Reumatología , Humanos , Reumatología/educación , Malasia/epidemiología , Reumatólogos , Enfermedades Musculoesqueléticas/diagnóstico , Enfermedades Musculoesqueléticas/epidemiología , Enfermedades Musculoesqueléticas/terapia , Atención a la SaludRESUMEN
The effect of biologic disease modifying anti-rheumatic drugs (bDMARDs) in treating rheumatoid arthritis (RA) in real-world clinical practice remains unknown in Southeast Asia. We aimed to assess the efficacy and safety of bDMARDs among Malaysian RA patients treated in routine clinical practice. A retrospective medical chart review of RA patients from 11 government hospitals were conducted from January 2003 to January 2014. A standardized questionnaire was used to abstract patient's demographic, clinical and treatment data. Level of disease activity was measured by DAS28 collected at baseline, 3, 6 and 12 months. Three hundred and one patients were available for analysis, mean age 41 (SD, 10.8) years, mean RA duration 12.3 (SD, 6.9) years and 98% had history of two or more conventional-synthetic DMARDs. There were 467 bDMARD courses prescribed with mean bDMARDs duration use of 12.9 months (SD 14.7). Tumour necrosis factor alpha inhibitors were the most common prescribed bDMARDs (77.1%), followed by Tocilizumab (14.6%) and Rituximab (8.4%). We observed significant improvement in mean DAS28 values from baseline to 3, 6 and 12 months (p < 0.001). Overall, 16.9% achieved DAS28 remission at 6 months. A third (35.6%) of patients reported adverse events, three commonest being infections (46.5%), allergy (22.9%) and laboratory abnormalities (12.9%). 3.7% of our patients had tuberculosis. Biologic DMARDs were effective in treating RA in real-world practice in Malaysia, despite a lower remission rate compared to developed countries. Except for higher rates of tuberculosis, the AEs were similar to the published reports.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Productos Biológicos/uso terapéutico , Adulto , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antirreumáticos/efectos adversos , Productos Biológicos/efectos adversos , Quimioterapia Combinada , Femenino , Humanos , Hipersensibilidad/etiología , Infecciones/etiología , Malasia , Masculino , Metotrexato/efectos adversos , Metotrexato/uso terapéutico , Persona de Mediana Edad , Estudios Retrospectivos , Rituximab/efectos adversos , Rituximab/uso terapéutico , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
BACKGROUND: Patient reported outcomes (PROs) are especially useful in assessing treatments for rheumatoid arthritis (RA) since they measure dimensions of health-related quality of life that cannot be captured using strictly objective physiological measures. The aim of this study was to compare the effects of combination etanercept and methotrexate (ETN + MTX) versus combination synthetic disease modifying antirheumatic drugs (DMARDs) and methotrexate (DMARD + MTX) on PRO measures among RA patients from the Asia-Pacific region, a population not widely studied to date. Patients with established moderate to severe rheumatoid arthritis who had an inadequate response to methotrexate were studied. METHODS: Patients were randomized to either ETN + MTX (N = 197) or DMARD + MTX (N = 103) in an open-label, active-comparator, multicenter study, with PRO measures designed as prospective secondary endpoints. The Health Assessment Questionnaire (HAQ), Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-Fatigue), Medical Outcomes Short Form-36 Health Survey (SF-36), Hospital Anxiety and Depression Scale (HADS) and the Work Productivity and Activity Impairment Questionnaire: General Health (WPAI:GH) were used. RESULTS: Significantly greater improvements were noted for the ETN + MTX group at week16 for HAQ mean scores and for proportion of patients achieving HAQ score ≤ 0.5, compared to patients in the DMARD + MTX group. SF-36 Summary Scores for physical and mental components and for 6 of 8 health domains showed significantly greater improvements at week16 for the ETN + MTX group; only scores for physical functioning and role-emotional domains did not differ significantly between the two treatment arms. Greater improvements at week16 were noted for the ETN + MTX group for FACIT-Fatigue, HADS, and WPAI:GH mean scores. CONCLUSION: Combination therapy using ETN + MTX demonstrated superior improvements using a comprehensive set of PRO measures, compared to combination therapy with usual standard of care DMARDs plus MTX in patients with established rheumatoid arthritis from the Asia-Pacific region. TRIAL REGISTRATION: clintrials.gov # NCT00422227.
Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Pueblo Asiatico , Inmunoglobulina G/uso terapéutico , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Adulto , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/etnología , Artritis Reumatoide/fisiopatología , Artritis Reumatoide/psicología , Asia/epidemiología , Pueblo Asiatico/psicología , Evaluación de la Discapacidad , Quimioterapia Combinada , Emociones , Etanercept , Femenino , Humanos , Inmunoglobulina G/efectos adversos , Masculino , Salud Mental , Metotrexato/uso terapéutico , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Recuperación de la Función , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVES: The prognostic significance of rheumatoid factor (RF) and anticyclic citrullinated peptide antibody (anti-CCP) in rheumatoid arthritis (RA) remains contentious due to the conflicting lines of evidence. This study aims to determine the association between RF isotypes and anti-CCP with disease severity in RA patients from three ethnic groups. METHODS: A total of 147 RA patients from three different ethnic groups (Malays, Chinese, and Indians) who fulfilled the 1987 American College of Rheumatology (ACR) revised criteria for RA were recruited into this study. The seroprevalence of RF isotypes immunoglobulin (Ig)A, IgG, and IgM, as well as anti-CCP was determined using commercial enzyme-linked immunosorbent assay (ELISA) kits. Multinomial regression analysis was performed to assess the independent effects of autoantibody status on the development of deforming and erosive RA and the presence of extra-articular manifestations (EAM). RESULTS: In Chinese patients, we found a significant association (p < 0.05) between IgG RF and anti-CCP and the presence of erosive disease, as well as IgM RF and IgG RF with the presence of joint deformities. In Indian patients, IgM RF was associated with deforming disease, whereas none of the antibodies were associated with disease severity in Malay patients. Multinomial regression analysis revealed that IgG RF was the most important predictor variable for erosive disease in Chinese patients, and IgM RF the only predictor variable associated with deforming disease in both Chinese and Indian RA patients. CONCLUSIONS: There is variability in the phenotypic association of RF isotypes and anti-CCP in relation to disease severity of RA in the three ethnic groups. RF, in particular, IgG and IgM, may be better prognosticators of severe disease in Chinese and Indian patients.
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Artritis Reumatoide/inmunología , Autoanticuerpos/análisis , Péptidos Cíclicos/inmunología , Factor Reumatoide/inmunología , Adulto , Anciano , Artritis Reumatoide/etnología , China/etnología , Estudios Transversales , Femenino , Humanos , India/etnología , Malasia/etnología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Seroepidemiológicos , Índice de Severidad de la EnfermedadRESUMEN
Methotrexate (MTX) is the most widely used disease-modifying anti-rheumatic drug (DMARD) for rheumatoid arthritis (RA). Many studies have attempted to understand the genetic risk factors that affect the therapeutic outcomes in RA patients treated with MTX. Unlike other studies that focus on the populations of Caucasians, Indian and east Asian countries, this study investigated the impacts of six single nucleotide polymorphisms (SNPs) that are hypothesized to affect the outcomes of MTX treatment in Malaysian RA patients. A total of 647 RA patients from three ethnicities (NMalay = 153; NChinese = 326; NIndian = 168) who received MTX monotherapy (minimum 15 mg per week) were sampled from three hospitals in Malaysia. SNPs were genotyped in patients using TaqMan real-time PCR assay. Data obtained were statistically analysed for the association between SNPs and MTX efficacy and toxicity. Analysis of all 647 RA patients indicated that none of the SNPs has influence on either MTX efficacy or MTX toxicity according to the Chi-square test and binary logistic regression. However, stratification by self-identified ancestries revealed that two out of six SNPs, ATIC C347G (rs2372536) (OR 0.5478, 95% CI 0.3396-0.8835, p = 0.01321) and ATIC T675C (rs4673993) (OR 0.5247, 95% CI 0.3248-0.8478, p = 0.008111), were significantly associated with MTX adequate response in RA patients with Malay ancestry (p < 0.05). As for the MTX toxicity, no significant association was identified for any SNPs selected in this study. Taken all together, ATIC C347G and ATIC T675C can be further evaluated on their impact in MTX efficacy using larger ancestry-specific cohort, and also incorporating high-order gene-gene and gene-environment interactions.
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Antirreumáticos , Artritis Reumatoide , Antirreumáticos/uso terapéutico , Artritis Reumatoide/inducido químicamente , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Humanos , Malasia , Redes y Vías Metabólicas , Metotrexato , Polimorfismo de Nucleótido SimpleRESUMEN
Chronic low back pain, defined as back pain lasting for more than three months, can be divided into mechanical or inflammatory back pain (IBP). IBP typically starts in patients below the age of 40, is improved with activity and worsens with rest. IBP is strongly associated with axial spondyloarthritis. Early recognition of IBP among primary care physicians is essential for timely diagnosis and intervention to ensure the best outcomes for patients with axial spondyloarthritis. This paper describes the Malaysian Society of Rheumatology's recently developed Inflammatory Back Pain Referral Algorithm for primary care physicians, which aims to facilitate the early identification and referral of IBP patients to rheumatologists.
RESUMEN
BACKGROUND: Fine-mapping of human leukocyte antigen (HLA) region for rheumatoid arthritis (RA) risk factors has identified several HLA alleles and its corresponding amino acid residues as independent signals (i.e., HLA-A, HLA-B, HLA-DPB1, and HLA-DQA1 genes), in addition to the well-established genetic factor in HLA-DRB1 gene. However, this was mainly performed in the Caucasian and East Asian populations, and data from different Asian regions is less represented. We aimed to evaluate whether there are independent RA risk variants in both anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA patients from the multi-ethnic Malaysian population, using the fine-mapping of HLA region strategy. METHODS: We imputed the classical HLA alleles, amino acids, and haplotypes using the Immunochip genotyping data of 1260 RA cases (i.e., 530 Malays, 259 Chinese, 412 Indians, and 59 mixed ethnicities) and 1571 controls (i.e., 981 Malays, 205 Chinese, 297 Indians, and 87 mixed ethnicities) from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) population-based case-control study. Stepwise logistic regression was performed to identify the independent genetic risk factors for RA within the HLA region. RESULTS: We confirmed that the HLA-DRB1 amino acid at position 11 with valine residue conferred the strongest risk effect for ACPA-positive RA (OR = 4.26, 95% CI = 3.30-5.49, PGWAS = 7.22 × 10-29) in the Malays. Our study also revealed that HLA-DRB1 amino acid at position 96 with histidine residue was negatively associated with the risk of developing ACPA-positive RA in the Indians (OR = 0.48, 95% CI = 0.37-0.62, PGWAS = 2.58 × 10-08). Interestingly, we observed that HLA-DQB1*03:02 allele was inversely related to the risk of developing ACPA-positive RA in the Malays (OR = 0.17, 95% CI = 0.09-0.30, PGWAS = 1.60 × 10-09). No association was observed between the HLA variants and risk of developing ACPA-negative RA in any of the three major ethnic groups in Malaysia. CONCLUSIONS: Our results demonstrate that the RA-associated genetic factors in the multi-ethnic Malaysian population are similar to those in the Caucasian population, despite significant differences in the genetic architecture of HLA region across populations. A novel and distinct independent association between the HLA-DQB1*03:02 allele and ACPA-positive RA was observed in the Malays. In common with the Caucasian population, there is little risk from HLA region for ACPA-negative RA.
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Artritis Reumatoide , Alelos , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/epidemiología , Artritis Reumatoide/genética , Autoanticuerpos/genética , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad/genética , Antígenos HLA , Cadenas HLA-DRB1/genética , HumanosRESUMEN
A total of 271 Southeast Asia Indians from Peninsular Malaysia were genotyped for HLA-A, -B, -C, -DRB1, and -DQB1 loci using polymerase chain reaction sequence-specific oligonucleotide probe hybridization methods. In this report, HLA-B and HLA-DQB1 was in Hardy-Weinberg proportions (HWEP) (p > 0.05). We observed significant deviation from the HWEP for HLA-A (p < 0.05), HLA-C (p < 0.01) and HLA-DRB1 (p < 0.01) loci. This genotype data is available in Allele Frequencies Network Database (AFND) Dos Santos et al. (2016).
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Etnicidad , Genotipo , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Cadenas beta de HLA-DQ/genética , Cadenas HLA-DRB1/genética , Alelos , Asia Sudoriental , Pueblo Asiatico , Frecuencia de los Genes , Genética de Población , Haplotipos , Humanos , India/etnología , Malasia/epidemiología , Malasia/etnologíaRESUMEN
A total of 194 Southeast Asia Chinese from Peninsular Malaysia were genotyped for HLA-A, -B, -C -DRB1, and -DQB1 loci using polymerase chain reaction sequence-specific oligonucleotide probe hybridization methods. In this report, the HLA-B, HLA-DRB1 and HLA-DQB1 were in Hardy-Weinberg proportions (HWEP) (pâ¯>â¯0.05). We observed significant deviation from HWEP in HLA-A (pâ¯<â¯0.05) and HLA-C (pâ¯<â¯0.01) loci. This genotype data was available in Allele Frequencies Network Database (AFND) Dos Santos et al. (2016).
Asunto(s)
Pueblo Asiatico , Genotipo , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Cadenas beta de HLA-DQ/genética , Cadenas HLA-DRB1/genética , Alelos , Asia Sudoriental , Frecuencia de los Genes , Genética de Población , Haplotipos , Prueba de Histocompatibilidad , Humanos , MalasiaRESUMEN
AIM: Vitamin D3 [25(OH)D] has been shown to be important in bone health and can influence rheumatoid arthritis (RA) disease activity. Vitamin D-binding protein (VDBP) levels vary with race and may modulate 'bioavailable' levels of 25(OH)D. The aim of this study was to explore the relationships between 25(OH)D, VDBP and clinical factors on bone mineral density (BMD) in a group of multi-ethnic Malaysian RA patients and healthy controls. METHODS: A cross-sectional study of 77 female RA patients and 29 controls was performed. Serum 25(OH)D was measured using the Elecsys® Vitamin D total assay. Serum VDBP was measured using a Quantikine® enzyme-linked immunosorbent assay kit. BMD was assessed using dual-energy X-ray absorptiometry (DXA). RESULTS: Overall, mean 25(OH)D levels were 42.66 ± 21.75 nmol/L with no significant difference between RA patients and controls. 25(OH)D levels were significantly higher in Chinese, compared to Malay/Indian subjects. In RA patients, menopausal status and body mass index (BMI) were significantly associated with BMD but not 25(OH)D or RA Disease Activity Score of 28 joints (DAS28). There was no significant correlation between 25(OH)D and DAS28, even after correction for menopausal status and BMI. VDBP levels were not significantly different between the races and did not significantly correlate with BMD, 25(OH)D overall, or DAS28 in RA patients. CONCLUSIONS: In Malaysian RA patients, menopausal status and BMI were more important influences on BMD than 25(OH)D or RA disease activity. The utility of measuring VDBP levels in this population remains uncertain.
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Artritis Reumatoide/sangre , Artritis Reumatoide/patología , Densidad Ósea , Proteína de Unión a Vitamina D/sangre , Vitamina D/análogos & derivados , Absorciometría de Fotón , Adulto , Anciano , Anciano de 80 o más Años , Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/etnología , Pueblo Asiatico , Biomarcadores/sangre , Índice de Masa Corporal , Estudios de Casos y Controles , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Malasia , Menopausia/sangre , Menopausia/etnología , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Vitamina D/sangreRESUMEN
A total of 951 Southeast Asia Malays from Peninsular Malaysia were genotyped for HLA-A, -B, -C -DRB1, and -DQB1 loci using polymerase chain reaction sequence-specific oligonucleotide probe hybridization methods. In this report, there were significant deviation from Hardy-Weinberg proportions for the HLA-A (p<0.0001), -B (p<0.0001), -DRB1 (p<0.0001) and -DQB1 (p<0.01) loci. Minor deviations from HWEP were detected for HLA-C (p=0.01). This genotype data was available in Allele Frequencies Network Database (AFND) Gonzalez-Galarza et al. (2015).
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Etnicidad , Antígenos HLA-A/genética , Antígeno HLA-B27/genética , Antígenos HLA-C/genética , Cadenas beta de HLA-DQ/genética , Cadenas HLA-DRB1/genética , Alelos , Asia Sudoriental , Bases de Datos de Ácidos Nucleicos , Frecuencia de los Genes , Genética de Población , Haplotipos , Humanos , Malasia/epidemiologíaAsunto(s)
Alopurinol/efectos adversos , Supresores de la Gota/efectos adversos , Retina/efectos de los fármacos , Enfermedades de la Retina/inducido químicamente , Adulto , Cristalización , Técnicas de Diagnóstico Oftalmológico , Femenino , Humanos , Retina/diagnóstico por imagen , Retina/fisiopatología , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/fisiopatología , Tomografía de Coherencia Óptica , Agudeza Visual/efectos de los fármacosRESUMEN
AIM: The purpose of this study is to compare the prevalence of rheumatoid factor (RF) isotypes and second generation anti-cyclic citrullinated peptides (anti-CCP) in Malaysian rheumatoid arthritis (RA) patients. METHODS: In this cross-sectional study, 147 established RA patients from three ethnic groups were recruited from a major rheumatology clinic in Malaysia. Enzyme-linked immunosorbent assays (ELISA) for serum RF isotypes IgA, IgG and IgM as well as second-generation anti-CCP were performed and the prevalence of each auto-antibody was compared in the three ethnic groups. RESULTS: The anti-CCP was the most prevalent auto-antibody in each of the ethnic groups, followed closely by RF IgM and RF IgG. Rheumatoid factor IgA was the least prevalent across all three ethnic groups. The anti-CCP-RF IgM combination provided the best test sensitivity. Seroprevalence of anti-CCP was strongly associated with the presence of each of the RF isotypes. The seroprevalence of RF and anti-CCP did not increase or decrease with advancing age, age at onset and disease duration. CONCLUSION: When used alone, anti-CCP provides a diagnostic advantage over RF IgM on the basis of test sensitivity. Considering the high cost of the anti-CCP assay, step-wise serum testing with IgM RF followed by anti-CCP may provide a more economically sensible option to optimize test sensitivity for RA.
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Anticuerpos Antiidiotipos/sangre , Artritis Reumatoide/inmunología , Autoanticuerpos/sangre , Péptidos Cíclicos/inmunología , Factor Reumatoide/inmunología , Adolescente , Adulto , Artritis Reumatoide/etnología , China/etnología , Femenino , Humanos , Isotipos de Inmunoglobulinas/sangre , India/etnología , Malasia/epidemiología , Masculino , Persona de Mediana Edad , Factor Reumatoide/sangre , Estudios Seroepidemiológicos , Adulto JovenRESUMEN
AIM: The aim of this study was to ascertain the management of gout by doctors in Malaysia. METHODS: A cross-sectional questionnaire survey was carried out among doctors attending rheumatology post-graduate courses, where gout was not a lecture topic. RESULTS: A total of 128 questionnaires were analyzed, of which the majority (67: 52.3%) were general practitioners. In the treatment of acute gout, 68.0% use non-selective non-steroidal anti-inflammatory drugs (NSAIDs), 53.9% use selective COX-2 inhibitors (coxibs), 66.4% use colchicine and 10.2% use allopurinol (ALLO). In the treatment of chronic gout, 36.7% use NSAIDs, 44.5% use coxibs, 19.5% use colchicine and 93% use ALLO. In both acute and chronic gout, corticosteroids (CS) are not used by over 90% of respondents. Fifty percent would stop ALLO during an acute attack. 95.3% do not start ALLO during an acute attack; 87.5% would start ALLO after the attack, with a median of 14 days afterwards. Once ALLO was started, 54.7% would continue indefinitely. Regarding target urate levels while on treatment, 10.9% would be satisfied with a high normal range, 21.9% middle of the range, 18.0% low normal range and 45.3% anywhere within the normal range. Fifteen percent would treat asymptomatic hyperuricemia. CONCLUSIONS: In Malaysia, anti-inflammatory agents are most commonly used for the treatment of acute and chronic gout, with corticosteroid usage at a low level. However, there are areas of concern regarding the diagnosis of gout and the usage of ALLO which are not consistent with current guidelines.
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Supresores de la Gota/uso terapéutico , Gota/tratamiento farmacológico , Atención Primaria de Salud , Práctica Profesional , Enfermedad Aguda , Alopurinol/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Enfermedad Crónica , Colchicina/uso terapéutico , Estudios Transversales , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Glucocorticoides/uso terapéutico , Gota/diagnóstico , Gota/fisiopatología , Humanos , Malasia , Atención Primaria de Salud/estadística & datos numéricos , Práctica Profesional/estadística & datos numéricos , Valores de Referencia , Encuestas y Cuestionarios , Ácido Úrico/sangreRESUMEN
In this study, three single nucleotide polymorphisms (SNPs) located within the promoter of the human interleukin (IL)-10 gene [rs1800896 (position: -1087G>A), rs1800871 (position: -824C>T) and rs1800872 (position: -597C>A)] were investigated in 84 rheumatoid arthritis (RA) patients and 95 age- and sex-matched healthy subjects using polymerase chain reaction-restriction fragment length polymorphism method. Production of IL-10 by peripheral blood lymphocytes from the RA patients and healthy subjects cultured in the presence of Concanavalin A (Con A) was determined by using enzyme-linked immunosorbent assay. The results show that the distribution of the IL-10 genotypes did not differ significantly between RA patients and healthy subjects (P>0.05). However, a significant difference was observed in allele frequencies of -824CT, -824TT, -597CA, and -597AA between the RA patients and healthy volunteers (P=0.04). The -1087A/-824T/-597A (ATA) haplotype, which comprises all mutant alleles, was associated with lower IL-10 production when compared with the other haplotypes. In contrast, the RA patients who did not display the ATA haplotype produced significantly higher levels of IL-10 when compared with those carrying either one (P=0.012) or two (P=0.005) ATA haplotypes. Our findings suggest that there is an association between SNPs in the promoter of the human IL-10 gene and susceptibility to RA.