A GA microsatellite in the Fli1promoter modulates gene expression and is associated with systemic lupus erythematosus patients without nephritisReportar como inadecuado




A GA microsatellite in the Fli1promoter modulates gene expression and is associated with systemic lupus erythematosus patients without nephritis - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Arthritis Research and Therapy

, 12:R212

First Online: 18 November 2010Received: 06 April 2010Revised: 07 October 2010Accepted: 18 November 2010

Abstract

IntroductionThe transcription factor Fli1 is implicated in the pathogenesis of systemic lupus erythematosus SLE. Recently, a GAn polymorphic microsatellite was characterized in the mouse Fli1 promoter that modulates promoter activity and is truncated in two lupus mouse models compared to non-autoimmune prone mice. In this work, we characterize a homologous GAn microsatellite in the human Fli1 promoter. The purpose of this study is to determine the effect of the microsatellite length on Fli1 promoter activity in vitro and to determine if the length of the GAn microsatellite is associated with SLE and-or specific disease characteristics.

MethodsConstructs with variable lengths of the GAn microsatellite in the Fli1 promoter were generated and analyzed in promoter-reporter P-R assays in a human T cell line. Using three SLE patient cohorts and matched controls, microsatellite length was measured and association with the presence of disease and the occurrence of specific disease manifestations was assessed.

ResultsP-R assays demonstrated that the presence of a shorter microsatellite resulted in higher Fli1 promoter activity. A significant association was observed in the lupus cohort SLE in Gullah Health SLEIGH between the GA26 base pair allele and absence of nephritis.

ConclusionsThis study demonstrates that a GAn microsatellite in the human Fli1 promoter is highly polymorphic. The length of the microsatellite is inversely correlated to Fli1 promoter activity in a human T cell line. Although no association between microsatellite length and lupus was observed, an association between a specific microsatellite length and patients without nephritis in the SLEIGH cohort was observed.

AbbreviationsCLUCarolina Lupus Study

CTCFCCCTC binding factor

PBMCsperipheral blood mononuclear cell

P-Rpromoter-reporter

SLESystemic Lupus Erythematosus

SLEIGHSystemic Lupus Erythematosus in Gullah Health.

Electronic supplementary materialThe online version of this article doi:10.1186-ar3189 contains supplementary material, which is available to authorized users.

Download fulltext PDF



Autor: Erin E Morris - May Y Amria - Emily Kistner-Griffin - John L Svenson - Diane L Kamen - Gary S Gilkeson - Tamara K Now

Fuente: https://link.springer.com/







Documentos relacionados