The interferon gene cluster: a candidate region for MS predisposition?

Miterski, Bianca; Jaeckel, S; Epplen, Jörg T.; Pöhlau, Dieter; Hardt, Cornelia

doi:10.1038/sj.gene.6363634

Cited by 25 publications

(18 citation statements)

References 29 publications

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“…Overall, these results implicate for the first time genetic variation in the IFN gene cluster with Th2-mediated diseases, whereas prior studies of a limited number of IFN variants have reported associations with Th1-mediated diseases, MS 40 and sarcoidosis. 47 Although we cannot exclude the possibility that some of these associations are due to typed or untyped coding variation, we note that the coding variation in the Hutterites appears to be confined to one or a few haplotypes.…”

Section: Discussionmentioning

confidence: 48%

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Variation in the type I interferon gene cluster on 9p21 influences susceptibility to asthma and atopy

et al. 2006

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A genome-wide screen for asthma and atopy susceptibility alleles conducted in the Hutterites, a founder population of European descent, reported evidence of linkage with a short tandem repeat polymorphism (STRP) within the type I interferon (IFN) gene cluster on chromosome 9p21. The goal of this study was to identify variation within the IFN gene cluster that influences susceptibility to asthma and atopic phenotypes. We screened approximately 25 kb of sequence, including the flanking sequence of all 15 functional genes and the single coding exon in 12, in Hutterites representing different IFNA-STRP genotypes. We identified 78 polymorphisms, and genotyped 40 of these (in 14 genes) in a large Hutterite pedigree. Modest associations (0.003oPo0.05) with asthma, bronchial hyper-responsiveness (BHR), and atopy were observed with individual variants or genes, spanning the entire 400 kb region. However, pairwise combinations of haplotypes between genes showed highly significant associations with different phenotypes (Po10 À5 ) that were localized to specific pairs of genes or regions of this cluster. These results suggest that variation in multiple genes in the type I IFN cluster on 9p22 contribute to asthma and atopy susceptibility, and that not all genes contribute equally to all phenotypes.

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Section: Discussionmentioning

confidence: 48%

“…Four of the exonic polymorphisms were previously reported: Asp57frameshift (171insA) and Ile184Arg in IFNA17, Cys20Stop in IFNA10, and Tyr51Tyr (153 C-T) in IFNB1. 39,40 Four nsSNPs reported in dbSNP were not present in the Hutterite screening set. These included one each in IFNA1 (rs2230050; freq.…”

Section: Sequence Variation and Patterns Of Ldmentioning

confidence: 99%

Variation in the type I interferon gene cluster on 9p21 influences susceptibility to asthma and atopy

et al. 2006

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“…All software used for this paper is available for downloading. 15 the phenotype frequency for IFNA1:07 was 6.3% (OR 12.41, P c o8 Â 10 À4 ). The combination TCRB-5/HLA-DRB1, which corresponds to TCRBV6S3*2 and HLA-DRB1*03, has been described previously.…”

Section: Ms Case -Control Studymentioning

confidence: 99%

“…Associations for the single alleles were reported previously. 14,15 ACs including this predisposing allele and a certain allele of another locus seem to be strongly associated with MS. However, the display of nOR (Figure 4c; single-count model) shows that most of these associations can be explained by the individual effect of the IFNA-1:07 allele.…”

Section: Simulation Studymentioning

confidence: 99%

Multilocus statistics to uncover epistasis and heterogeneity in complex diseases: revisiting a set of multiple sclerosis data

et al. 2003

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New statistics are developed to gather the contribution of many alleles at different loci to common diseases. Both inferential and descriptive statistics are included in order to uncover epistatic effects as well as heterogeneity. The problem of multiple testing is circumvented by considering a global null hypothesis. Global testing is supplemented by descriptive methods that make use of measures like odds ratio or the Pvalue of individually tested allele combinations. Visualization helps to reflect complex data sets. The methods described here have been scrutinized by statistical simulations, and we show that power gains can be substantial as compared to single locus statistics. Typing data of multiple sclerosis patients and controls are investigated, representing an example of larger scale information in screening candidate genes for their impact on complex diseases. New insights emerge from this data set demonstrating genetic heterogeneity and evidence for epistasis.

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“…Research in the German population excluded the IFN-␤ gene as a candidate for MS predisposition, but suggested the existence of predisposing IFN-␣ genes. 23,24 Furthermore, the family of interferon regulatory factors constitutes clearly a very interesting target for future studies, as some of its members are located within or near chromosomal regions exhibiting significant linkage to MS. To these belong IRF2 at 4q35.1, IRF3 at 19q13.3-13.4 and IRF4 at 6p23-25. Among these, the IRF2 locus in particular is worth further study, since enhanced expression of IRF-2 in acute MS lesions as compared to normal white matter was recently uncovered by means of cDNA microarray technology.…”

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confidence: 99%

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

et al. 2000

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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.

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The interferon gene cluster: a candidate region for MS predisposition?

Cited by 25 publications

References 29 publications

Variation in the type I interferon gene cluster on 9p21 influences susceptibility to asthma and atopy

Variation in the type I interferon gene cluster on 9p21 influences susceptibility to asthma and atopy

Multilocus statistics to uncover epistasis and heterogeneity in complex diseases: revisiting a set of multiple sclerosis data

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

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