Genomic Polymorphism at the Interferon-Induced Helicase (IFIH1) Locus Contributes to Graves’ Disease Susceptibility

Sutherland, Alison; Davies, Jocelyn; Owen, Catherine J.; Vaikkakara, Suresh; Walker, Claire; Cheetham, Timothy; James, Robert A.; Perros, Petros; Donaldson, Peter; Cordell, Heather J.; Quinton, Richard; Pearce, Simon H. S.

doi:10.1210/jc.2007-0173

Cited by 105 publications

(90 citation statements)

References 19 publications

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“…The IFIH1 gene has been implicated as a susceptibility gene in other autoimmune diseases, such as type I diabetes 17 or Graves' disease. 18 Common genetic variants have been implicated in various autoimmune diseases or in families with several cases affected by different diseases. 19,20 It is of interest to note that the IFIH1-GCA-KCNH7 locus was not a region of interest in a recent first genome-wide association scan in MS.…”

Section: Discussionmentioning

confidence: 99%

IFIH1-GCA-KCNH7 locus is not associated with genetic susceptibility to multiple sclerosis in French patients

et al. 2009

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A recent investigation reported, for the first time, an association between variants in the IFIH1-GCA-KCNH7 locus and multiple sclerosis (MS). We sought to replicate this genetic association in MS with a new independent MS cohort composed of French Caucasian MS trio families. The two most significant IFIH1 single nucleotide polymorphisms, rs1990760 and rs2068330, reported as involved in MS susceptibility, were genotyped in 591 French Caucasian MS trio families, and analyzed using the transmission/disequilibrium test. No association with MS was found (rs1990760, P ¼ 0.45 and rs2068330, P ¼ 0.27). Similarly, no significant association was detected after stratification for HLA-DRB1*1501 carriers. Reasons that may explain this discrepancy between the original report and our study are discussed.

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Section: Discussionmentioning

confidence: 99%

IFIH1-GCA-KCNH7 locus is not associated with genetic susceptibility to multiple sclerosis in French patients

et al. 2009

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“…The effect found for MS was of similar magnitude to the one originally described regarding T1D 3 and also present in Graves' disease. 8 Strong linkage disequilibrium within this locus precluded us from further dissecting where the etiologic gene resides. The polymorphism rs1990760 in the IFIH1 gene was proposed as the causal variant based on the conservation of aligned sequences in mammals.…”

Section: Discussionmentioning

confidence: 99%

“…7 More recently, association of this locus with Grave's disease was also found. 8 We aimed at identifying whether this chromosomal region was a common susceptibility locus for other autoimmune disease as MS.…”

Section: Introductionmentioning

confidence: 99%

IFIH1-GCA-KCNH7 locus: influence on multiple sclerosis risk

et al. 2008

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A recent genome-wide scan of nonsynonymous SNPs and ulterior validation in case-control and family analyses evidenced a susceptibility locus for type 1 diabetes (T1D) on chromosome 2q24.3. We aimed at testing the effect of this locus in other autoimmune diseases with complex genetic background, such as multiple sclerosis (MS). Four SNPs along the locus, rs13422767, rs2111485, rs1990760 and rs2068330, were genotyped using TaqMan MGB chemistry in 311 T1D and 412 MS patients and 535 ethnically matched healthy controls. The previously reported association of this locus was found for the first time in MS (rs2068330, G vs C: P ¼ 0.001; OR (95% CI) ¼ 0.73 (0.6-0.88)) and a trend for replication was observed in our Spanish diabetic cohort. Therefore, genes included in this locus -IFIH1 interferon induced helicase, GCA grancalcin or the potassium channel KCNH7 -are potential candidates implicated in the pathogenesis of these autoimmune diseases, although strong linkage disequilibrium in the region hampered further localization of the etiologic gene.

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“…Interestingly, some studies have shown strong associations between the rs1990760 polymorphism of the IFIH1 gene and other autoimmune diseases, such as psoriasis (63,64), chronic periodontitis (63), polymyositis (65), multiple sclerosis (57,66), systemic lupus erythematosus (67), and Graves' disease (68).…”

Section: Associations Between Ifih1 and Other Autoimmune Conditionsmentioning

confidence: 99%

The role of interferon induced with helicase C domain 1 (IFIH1) in the development of type 1 diabetes mellitus

Bouças

Oliveira

Canani

et al. 2013

Arq Bras Endocrinol Metab

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Type 1 diabetes mellitus (T1DM) is a chronic, progressive, autoimmune disease characterized by metabolic decompensation frequently leading to dehydration and ketoacidosis. Viral pathogens seem to play a major role in triggering the autoimmune destruction that leads to the development of T1DM. Among several viral strains investigated so far, enteroviruses have been consistently associated with T1DM in humans. One of the mediators of viral damage is the double-stranded RNA (dsRNA) generated during replication and transcription of viral RNA and DNA. The IFIH1 gene encodes a cytoplasmic receptor of the pattern-recognition receptors (PRRs) family that recognizes dsRNA, playing a role in the innate immune response triggered by viral infection. Binding of dsRNA to this PRR triggers the release of proinflammatory cytokines, such as interferons (IFNs), which exhibit potent antiviral activity, protecting uninfected cells and inducing apoptosis of infected cells. The IFIH1 gene appears to play a major role in the development of some autoimmune diseases, and it is, therefore, a candidate gene for T1DM. Within this context, the objective of the present review was to address the role of IFIH1 in the development of T1DM. Arq Bras Endocrinol Metab. 2013;57(9):667-76 Keywords Autoimmunity; type 1 diabetes mellitus; viral infection; IFIH1 RESUMO O diabetes melito tipo 1 (T1DM) é uma doença autoimune crônica e progressiva caracterizada por descompensações metabólicas frequentemente acompanhadas por desidratação e cetoacidose. Os agentes virais parecem ter um papel importante no desencadeamento da destruição autoimune que leva ao desenvolvimento do T1DM. Entre as cepas virais estudadas até agora, a família dos enterovírus foi consistentemente associada ao surgimento da doença em humanos. Um dos mediadores do dano viral é o RNA fita dupla (RNAfd) gerado durante a replicação e transcrição de RNA e DNA viral. O gene IFIH1 codifica um receptor citoplasmático pertencente à família dos pattern-recognition receptors (PRRs) que reconhece o RNAfd, tendo um papel importante na resposta imune inata desencadeada por infecção viral. A ligação do RNAfd a essa PRR desencadeia a liberação de citocinas pró-inflamatórias como interferons (IFNs), os quais exibem uma potente ação antiviral e têm como objetivo proteger as células não infectadas e induzir apoptose naquelas já contaminadas. O gene IFIH1 parece ter uma participação importante no desenvolvimento de algumas doenças autoimunes. Por isso, esse gene é um candidato ao desenvolvimento do T1DM. Dentro desse contexto, o objetivo da presente revisão foi abordar o papel do IFIH1 no desenvolvimento do T1DM. Arq Bras Endocrinol Metab.2013;57(9):667-76 Descritores Autoimunidade; diabetes melito tipo 1; infecção viral; IFIH1

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Genomic Polymorphism at the Interferon-Induced Helicase (IFIH1) Locus Contributes to Graves’ Disease Susceptibility

Abstract: We confirm a significant contribution of the Ala946Thr IFIH1 polymorphism to organ-specific autoimmune diseases, extending the range of conditions associated with this variant to include Graves' disease. This polymorphism may also contribute to several other autoimmune disorders.

Cited by 105 publications

References 19 publications

IFIH1-GCA-KCNH7 locus is not associated with genetic susceptibility to multiple sclerosis in French patients

IFIH1-GCA-KCNH7 locus is not associated with genetic susceptibility to multiple sclerosis in French patients

IFIH1-GCA-KCNH7 locus: influence on multiple sclerosis risk

The role of interferon induced with helicase C domain 1 (IFIH1) in the development of type 1 diabetes mellitus

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