Lack of association between the interferon regulatory factor-1 (IRF1) locus at 5q31.1 and multiple sclerosis in Germany, Northern Italy, Sardinia and Sweden

Abstract

Interferon regulatory factor-1 (IRF-1) is a transcriptional inducer of the interferon-␤ (IFN-␤) gene and other interferonstimulated genes. A GT repeat polymorphism in the 7th intron of the IRF-1 gene was used as a marker to test for association with multiple sclerosis (MS) in a case-control study including individuals from Germany, Northern Italy and Sweden. In none of these populations, did we find any significant allelic association with disease. This lack of association was confirmed by testing transmission disequilibrium of individual IRF1 alleles in a representative sample of Sardinian simplex MS families. No deviation of the expected 50% transmission rates was seen. Therefore, our work does not provide evidence in favor of IRF1 being a candidate for conferring genetic susceptibility to, or protection against, MS in Europe. Genes and Immunity (2000) 1, 290-292.

Suppression of EAE by oral tolerance is independent of endogenous IFN‐β whereas treatment with recombinant IFN‐β ameliorates EAE

“…This could partly be the result of genetic heterogeneity of the MS patients, especially in regard to the functional IFN‐β gene. In agreement, genetic association studies have reported controversial linkage associations between MS and genetic loci for type I IFNs or other type I signaling‐related genes 41 , 42 , 43 , 44 , 45 . Naturally, we asked whether EAE in B10RIII genetic background could differ in its respond to IFN‐β reatment.…”

“…In agreement, genetic association studies have reported controversial linkage associations between MS and genetic loci for type I IFNs or other type I signaling-related genes. [41][42][43][44][45] Naturally, we asked whether EAE in B10RIII genetic background could differ in its respond to IFN-b reatment. Not unexpectedly, exogenous administration of recombinant IFN-b to IFN-b +/+ mice resulted in significant amelioration of EAE.…”

A multilayer perceptron neural network-based approach for the identification of responsiveness to interferon therapy in multiple sclerosis patients

“…Key steps in the IFN-b signaling pathway are phosphorylation of IFN receptors (IFNAR-1 and IFNAR-2 subunits) by the Janus kinases JAK1 and TYK2 followed by recruitment, activation and release in the cytosol of STAT-1 and STAT-2 proteins, which, together with nuclear p48/IRF-9, form an active transcription factor that translocates into the nucleus, where it promotes induction of such genes as IRF-1 [4]. Experimental evidence suggests that genetic variations in the IFN signaling pathway could be involved in MS susceptibility [7,16], but studies of a link between these variations and IFN therapy outcome have yielded inconclusive results [16,30,23,31]. The aim of our study was to try to identify gene polymorphisms in the main genes involved in IFN's mechanism of action that might distinguish between responder and non-responder MS patients.…”

Associations between interferon regulatory factor–1 polymorphisms and Behçet’s disease

“…IRF-1 polymorphisms have been studied in patients with type 1 diabetes mellitus [9], asthma [10], celiac disease [11], juvenile idiopathic arthritis (JIA) [12], multiple sclerosis [13], Graves' disease [14], hepatitis virus C (HCV) infection [15], and uterine cervical cancer [16]. In addition, IRF-1 promoter functional polymorphisms have been found to be associated with antiviral activity against hepatitis C infection [17,18], and the 3=-untranslated region (UTR) polymorphism was suggested to be associated with disease susceptibility to JIA [12].…”