Rheumatoid Arthritis: Granados J

Delgado-Vega AM, Martín J, Granados J, Anaya JM. · Unidad de Biología Celular e Inmunogenética, Corporación para Investigaciones Biológicas (CIB), Universidad del Rosario, Medellín, Colombia. · Biomedica. · Pubmed #17315483 No free full text.

Abstract: Rheumatoid arthritis is a chronic and systemic autoimmune disease characterized by inflammation and destruction of the synovial joints. It affects approximately 0.5% of the Latin-American population and is three times more common in women than in men. Evidence of familial aggregation (lambdas=2-17) was the first indication of a genetic susceptibility to disease. As in other autoimmune diseases, it has a complex genetic basis. Results from whole-genome scans indicate that the HLA region contains a significant and consistent set of linked loci. However, HLA accounts for only one-third of the genetic susceptibility of disease, indicating that non-HLA genes are also involved in the disease susceptibility. In Latin-America, association with HLA-DRB1*0404 and TNF -308A alleles has been uniformly established; however, many other candidate genes remain to be studied. The identification of genetic factors conferring susceptibility to rheumatoid arthritis will contribute to the knowledge of the pathogenic mechanisms, ability to predict its occurrence, the development of diagnostic tools, prognosis, and treatment. The genetic epidemiology of rheumatoid arthritis is herein reviewed; a set of recommendations is provided for the design, analysis and interpretation of genetic association studies in the context of Latin-American populations.

Villa AR, Kraus A, Jiménez-Corona A, Sandino S, Velázquez-González A, Granados J, Alarcón-Segovia D. · The Clinical Epidemiology Unit. · J Clin Rheumatol. · Pubmed #19078467 No free full text.

Abstract: ABSTRACT: Relationships between autoimmune rheumatic diseases and malignant neoplasms have been discussed, but there is no study of the different rheumatic diseases examining the risk of developing cancer. Our study has examined probabilities for developing malignancy among patients with connective tissue diseases seen in a single institution. Patients with autoimmune rheumatic disease and malignancy were compared with patients with the same autoimmune rheumatic diseases without malignancy. All cases identified through record-linkage from 1964 to 1996 were selected. Four controls per case were randomly selected from a pool of 3228 patients. The rheumatic diseases considered were rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), primary Sjögren's syndrome (pSS), dermatomyositis-polymyositis (DM-PM), and systemic sclerosis (Scl). The statistical analysis was conducted by conditional logistic regression, testing rheumatic disease as main effect. We identified 72 cases and 288 controls. Fifty-three of the cases had solid tumors, and 19 had lymphoproliferative neoplasms. The risk of developing a malignancy was considerably higher in DM-PM than in SLE (odds ratio [OR] = 17.5, 95% confidence interval [CI] 4.1-75.7), in pSS than in SLE (OR = 5.7, 95% CI 2.2-15.1), and in Scl than in SLE (OR = 5.4, 95% CI 1.6-18.0). These risks persisted after controlling for rheumatic disease duration, the time the disease was active, and anti-rheumatic treatment. RA had an OR of 1.8 (95% CI 0.9-3.4) with respect to SLE. This is the first study which describes the magnitude of risks among rheumatic diseases associated with the probability of developing a malignant neoplasm whether lymphoproliferative or solid. The risks in this series depend on the primary rheumatic disease, with DM-PM, pSS, and Scl all having greater risk than SLE.

Sáez-de-Ocariz M, Granados J, Yamamoto-Furusho JK, López-Martínez A, Vega-Memije ME. · Department of Dermatology, Hospital Dr Manuel Gea González, Mexico City, Mexico. · Skinmed. · Pubmed #17786108 links to  free full text

This publication has no abstract.

Rodríguez-Carreón AA, Zúñiga J, Hernández-Pacheco G, Rodríguez-Pérez JM, Pérez-Hernández N, Montes de Oca JV, Cardiel MH, Granados J, Vargas-Alarcón G. · Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico. · J Autoimmun. · Pubmed #15725578 No free full text.

Abstract: The aim of this study was to determine the frequency and potential relevance of the promoter polymorphisms of the tumor necrosis factor-alpha (TNF-alpha) in the severity of rheumatoid arthritis (RA) in Mexicans. HLA-DR and polymorphisms at positions -238 and -308 of TNF-alpha gene were determined in 137 Mexican RA patients (44 with severe and 93 with non-severe RA) as well as in 169 healthy controls (99 were typed for HLA-DR). We observed an increased frequency of HLA-DR4 in severe RA compared to healthy controls (pC=0.02, OR=2.33). TNF polymorphism analysis showed a significant increased frequency of TNF -238 GG genotype in the whole group of RA patients when compared to healthy controls (pC=0.007, OR=4.71). When the analyses were carried out separately in severe and non-severe RA patients, the increased frequency of -238 GG genotype only was observed in patients with non-severe forms of the disease. Analysis of -308 polymorphism showed increased frequency of -308 T2 (A) allele in severe RA when compared to non-severe disease (pC=0.011, OR=3.29) and to healthy controls (pC=0.002, OR=3.97). The data demonstrate that -308 T2 (A) allele is associated with susceptibility to develop severe RA in Mexicans. This association could be independent from HLA-DR alleles and might be used as a prognostic marker for severe RA.

Ruiz-Morales JA, Vargas-Alarcón G, Flores-Villanueva PO, Villarreal-Garza C, Hernández-Pacheco G, Yamamoto-Furusho JK, Rodríguez-Pérez JM, Pérez-Hernández N, Rull M, Cardiel MH, Granados J. · Department of Immunology and Rheumatology (J.A.R.-M., C.V.-G., J.K.Y.-F., M.R., M.H.C., J.G.), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico. · Hum Immunol. · Pubmed #15041166 No free full text.

Abstract: The risk to develop rheumatoid arthritis (RA) has been associated with the presence of HLA-DRB1 alleles encoding the "shared epitope" (SE). Additionally, HLA-DRB1 alleles encoding an aspartic acid at position 70 (D70+ ) have been associated with protection against the development of RA. In this study we tested the association between either SE or D70+ and rheumatoid arthritis in Mexican Mestizos. We included 84 unrelated Mexican Mestizos patients with RA and 99 unrelated healthy controls. The HLA-typing was performed by PCR-SSO and PCR-SSP. We used the chi-squared test to detect differences in proportions of individuals carrying at least one SE or D70+ between patients and controls. We found that the proportion of individuals carrying at least one HLA-DRB1 allele encoding the SE was significantly increased in RA cases as compared to controls (p(c) = 0.0004, OR = 4.1, 95% CI = 2.2-7.7). The most frequently occurring allele was HLA-DRB1*0404 (0.161 vs 0.045). Moreover, we observed a significantly increased proportion of HLA-DRB1 SE+ cases with RF titers above the median (p = 0.005). Conversely, the proportion of individuals carrying at least one HLA-DRB1 allele encoding the D70+ was significantly decreased (p(c) = 0.004, OR = 0.4, 95% CI 0.2-0.7) among RA patients compared with controls. In conclusion, the SE is associated with RA in Mexican Mestizos as well as with the highest titers of RF.

Zúñiga JA, Villarreal-Garza C, Flores E, Barquera R, Pérez-Hernández N, Montes de Oca JV, Cardiel MH, Vargas-Alarcón G, Granados J. · Molecular Biology and Immunogenetics Laboratory, Infectious Diseases Unit, Instituto Nacional de Enfermedades Respiratorias, Calzada Tlalpan 4502, Tlalpan 14080, Mexico, D.F. · Clin Exp Rheumatol. · Pubmed #12846056 No free full text.

Abstract: OBJECTIVE: The aim of this study was to analyze the frequencies of the CCR5 delta 32 deletion and HLA class II alleles in Mexican Amerindian populations and its relevance in the development and severity of RA. METHODS: We studied 212 Mexican Mestizo subjects (40 patients with refractory RA, 102 patients with non-refractory RA and 70 healthy individuals). At the same time, to evaluate the ethnicity of the CCR5 delta 32 deletion we also studied 192 individuals from three Mexican Amerindian populations (70 Mayo (Capomo) individuals, 61 Teenek individuals, and 61 Mazatecan Indians). The delta 32 deletion in the CCR5 structural gene and HLA-DRB1 were determined by a PCR-SSP and a PCR-SSO procedure, respectively. RESULTS: In the non-refractory RA group the CCR5 delta 32 gene frequency was 0.019 and the following genotype frequencies were observed: CCR5/CCR5 = 98.0%, CCR5/CCR5 delta 32 = 1.9% and CCR5 delta 32/CCR5 delta = 1.0%. In the refractory RA group the CCR5 delta 32 gene frequency was 0.025 and the genotype distribution was similar to that in the non-refractory RA group. The deletion was not detected in the Mexican Mestizo healthy group, or among the Teenek and Mayo Amerindians, all being individuals homozygous for the wild type allele. In the Mazatecan group the deletion frequency was 1.6% (g.f. = 0.016). We observed a significant increase in the frequency of the DRB1*07 allele in severe RA patients in relation to the non-severe RA group (p = 0.02, OR = 5.65, 95% CI = 0.95-43.05). CONCLUSION: Our results suggest that the CCR5 delta 32 deletion is not common in Mexican Amerindian populations and this study does not support an important role of CCR5 delta 32 in the pathogenesis of RA or a severe form of the disease in Mexicans.

Simón JA, Granados J, Cabiedes J, Morales JR, Varela JA. · Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, CP, México DF. · Lupus. · Pubmed #12090562 No free full text.

Abstract: The coexistence of systemic lupus erythematosus and rheumatoid arthritis (rhupus), is a rare clinical condition. To date, 50 cases of rhupus have been described worldwide; however, the lack of clinical criteria for this rheumatic condition has created confusion in the characterization of this disorder. Nevertheless, in this paper we describe a comprehensive clinical and serological characterization of a cohort of 22 Mexican patients with rhupus, supported by generic HLA-DR phenotyping. We found that rhupus patients have a special clinical behavior. In this setting, the signs and symptoms of rheumatoid arthritis prevail, little organic damage associated with systemic lupus erythematosus (SLE) exists and none of the cases present thrombosis or morbidity during pregnancy in spite of presenting a high frequency of anticardiolipin antibodies. We also found an increased frequency of HLA-DR1 and HLA-DR2 alleles compared to healthy ethnically matched controls, systemic lupus erythematosus and rheumatoid arthritis patients.

Jakez-Ocampo J, Richaud-Patin Y, Granados J, Sánchez-Guerrero J, Llorente L. · No affiliation provided · Arthritis Rheum. · Pubmed #14872469 links to  free full text

This publication has no abstract.