ABSTRACT
OBJECTIVE: To assess whether genetically determined Amerindian ancestry predicts increased presence of risk alleles of known susceptibility genes for systemic lupus erythematosus (SLE). METHODS: Single-nucleotide polymorphisms (SNPs) within 16 confirmed genetic susceptibility loci for SLE were genotyped in a set of 804 Mestizo lupus patients and 667 Mestizo healthy controls. In addition, 347 admixture informative markers were genotyped. Individual ancestry proportions were determined using STRUCTURE. Association analysis was performed using PLINK, and correlation between ancestry and the presence of risk alleles was analyzed using linear regression. RESULTS: A meta-analysis of the genetic association of the 16 SNPs across populations showed that TNFSF4, STAT4, ITGAM, and IRF5 were associated with lupus in a Hispanic Mestizo cohort enriched for European and Amerindian ancestry. In addition, 2 SNPs within the major histocompatibility complex region, previously shown to be associated in a genome-wide association study in Europeans, were also associated in Mestizos. Using linear regression, we predicted an average increase of 2.34 risk alleles when comparing an SLE patient with 100% Amerindian ancestry versus an SLE patient with 0% Amerindian ancestry (P < 0.0001). SLE patients with 43% more Amerindian ancestry were predicted to carry 1 additional risk allele. CONCLUSION: Our results demonstrate that Amerindian ancestry is associated with an increased number of risk alleles for SLE.
Subject(s)
American Indian or Alaska Native/ethnology , American Indian or Alaska Native/genetics , Gene Frequency/genetics , Genetic Predisposition to Disease/ethnology , Genetic Predisposition to Disease/genetics , Lupus Erythematosus, Systemic/ethnology , Lupus Erythematosus, Systemic/genetics , CD11b Antigen/genetics , Case-Control Studies , Humans , Interferon Regulatory Factors/genetics , Latin America , Linear Models , OX40 Ligand/genetics , Polymorphism, Single Nucleotide/genetics , Risk Factors , STAT4 Transcription Factor/geneticsABSTRACT
Introducción: En un reciente estudio, se demostró una alta reactividad negativa al PPD o tuberculina en pacientes con artritis reumatoide (AR), (70%) comparado con controles (30%). Para determinar si esta alta reactividad negativa al PPD está asociada con un determinado patrón de citocinas, se compararon las concentraciones séricas de interleucina (IL)-2, IL-4, IL-6, IL-10, factor de necrosis tumoral (TNF)-a e interferón (IFN)-g en pacientes con AR con reactividad positiva y negativa al PPD. Se analizó también la correlación entre las citocinas y la actividad de la AR. Material y métodos: Se estudiaron 40 pacientes con AR y 21 individuos sanos. Se consideró reactividad positiva al PPD a una induración e 5mm y reactividad negativa cuando es < 5 mm. La actividad de la AR se determinó según el DAS28. Las citocinas se determinaron por citometría de flujo utilizando el Kit Multiplex Cytometric Bead Array. Resultados: De los pacientes con AR, 27 (67,5%) presentaron reactividad negativa al PPD y 13 (32,5%) reactividad positiva al PPD, similares en edad, sexo femenino y enfermedad activa. No se encontraron diferencias significativas en las citocinas entre los grupos con PPD positivo y PPD negativo. El IFN-g (r = 0,433; p = 0,005) y la IL-6 (r = 0,325; p = 0,041) fueron las únicas que mostraron correlación positiva con la actividad de la enfermedad. Conclusiones: No parece que haya diferencias en el patrón de citocinas séricas en los pacientes con reactividad negativa y positiva al PPD(AU)
Introduction: We demonstrated, in a recently published study, far more PPD negative reactivity among patients who had RA (70%) than among controls (30%). To evaluate the hypothesis that different response to PPD in RA patients is associated with different profiles of serum cytokines, we compared the serum levels of IL-2, IL-4, IL-6, IL-10, TNF alpha and IFN gamma from PPD negative and PPD positive RA patients. We also evaluated any correlations between serum cytokines and RA activity. Material and methods: Forty RA patients and 21 controls were enrolled.Those with an induration < 5mm were considered as negative and those with e 5mm as positive PPD. Disease activity was calculated using DAS28. Plasma levels of cytokines were determined using the multiplex BD TM Cytometric Bead Array Kit Assay. Results: Of the RA patients, 27 (67.5%) had negative reaction to PPD and 13 (32.5%) a positive reaction to PPD. There was no statistical difference in sex profile, age or activity index between both negative and positive PPD RA patients. There was no significant difference in all the cytokines measured between PPD positive and PPD negative RA patients. Index activity show a positive correlation with IFN gamma (r = 0.433; p = 0.005) and IL-6 (r = 0.325; p = 0.041) in RA patients. Conclusions: Positive and negative tuberculin RA patients seem to show a similar cytokine serum profile(AU)
Subject(s)
Humans , Arthritis, Rheumatoid/physiopathology , Cytokines/blood , Tuberculin , Case-Control Studies , Interleukins/blood , Tumor Necrosis Factors/bloodABSTRACT
INTRODUCTION: We demonstrated, in a recently published study, far more PPD negative reactivity among patients who had RA (70%) than among controls (30%). To evaluate the hypothesis that different response to PPD in RA patients is associated with different profiles of serum cytokines, we compared the serum levels of IL-2, IL-4, IL-6, IL-10, TNF alpha and IFN gamma from PPD negative and PPD positive RA patients. We also evaluated any correlations between serum cytokines and RA activity. MATERIAL AND METHODS: Forty RA patients and 21 controls were enrolled. Those with an induration < 5mm were considered as negative and those with ≥ 5mm as positive PPD. Disease activity was calculated using DAS28. Plasma levels of cytokines were determined using the multiplex BD TM Cytometric Bead Array Kit Assay. RESULTS: Of the RA patients, 27 (67.5%) had negative reaction to PPD and 13 (32.5%) a positive reaction to PPD. There was no statistical difference in sex profile, age or activity index between both negative and positive PPD RA patients. There was no significant difference in all the cytokines measured between PPD positive and PPD negative RA patients. Index activity show a positive correlation with IFN gamma (r = 0.433; p = 0.005) and IL-6 (r = 0.325; p = 0.041) in RA patients. CONCLUSIONS: Positive and negative tuberculin RA patients seem to show a similar cytokine serum profile.
