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The IFIH1/MDA5 rs1990760 Gene Variant (946Thr) Differentiates Early Versus Late-Onset Skin Disease and Increased the Risk of Arthritis in a Spanish Cohort of Psoriatic Disease
Coto-Segura, P.; Vázquez-Coto, D.; Velázquez-Cuervo, L.; García-Lago, C.; Coto, E.; Queiro, R. The IFIH1/MDA5 rs1990760 Gene Variant (946Thr) Differentiates Early- versus Late-Onset Skin Disease and Increases the Risk of Arthritis in a Spanish Cohort of Psoriasis. Int. J. Mol. Sci.2023, 24, 14803.
Coto-Segura, P.; Vázquez-Coto, D.; Velázquez-Cuervo, L.; García-Lago, C.; Coto, E.; Queiro, R. The IFIH1/MDA5 rs1990760 Gene Variant (946Thr) Differentiates Early- versus Late-Onset Skin Disease and Increases the Risk of Arthritis in a Spanish Cohort of Psoriasis. Int. J. Mol. Sci. 2023, 24, 14803.
Coto-Segura, P.; Vázquez-Coto, D.; Velázquez-Cuervo, L.; García-Lago, C.; Coto, E.; Queiro, R. The IFIH1/MDA5 rs1990760 Gene Variant (946Thr) Differentiates Early- versus Late-Onset Skin Disease and Increases the Risk of Arthritis in a Spanish Cohort of Psoriasis. Int. J. Mol. Sci.2023, 24, 14803.
Coto-Segura, P.; Vázquez-Coto, D.; Velázquez-Cuervo, L.; García-Lago, C.; Coto, E.; Queiro, R. The IFIH1/MDA5 rs1990760 Gene Variant (946Thr) Differentiates Early- versus Late-Onset Skin Disease and Increases the Risk of Arthritis in a Spanish Cohort of Psoriasis. Int. J. Mol. Sci. 2023, 24, 14803.
Abstract
The melanoma differentiation-associated protein 5 (MDA5; encoded by the IFIH1 gene) mediates the activation of the interferon pathway in response to viral infection. This protein is also upregulated in autoimmune diseases and psoriasis skin lesions. IFIH1 gene variants that increased the MDA5 activity have been associated with increased risk for immune mediated diseases, including psoriasis. Our aim was to determine the association between three IFIH1 variants (rs35337543, intron8 +1G>C; rs35744605, Glu627Stop; and rs1990760, Ala946Thr) and the main clinical findings in a cohort of Spanish patients with psoriatic disease (N=572; 77% early-onset). Early-onset psoriasis (EOPs) had a significant higher frequency of severe disease and Cw6+. Carriers of the 946Thr variant were more common in EOPs (p<0.001), and the effect was more pronounced among Cw6-negatives. This variant was also associated with an increased risk of psoriatic arthritis (PsA) independently of other factors (OR=1.62, 95%CI=1.11-2.37). The rs3533754 and rs35744605 have been reported as risk factors for viral infection and protective for autoimmune diseases, but we did not find significant differences between the two onset age or PsA groups. However, due to the reduced frequency of the two variants (<0.02) the size of our cohort was too low to conclude a significant effect.
In conclusion, the common IFIH1 rs1990760 T allele that has been linked to increased gene expression was significantly more frequent in EOPs patients. This variant was also an independent risk factor for PsA in our cohort. This risk allele was in linkage disequilibrium with other variants previously associated with the risk of psoriasis and PsA. Our study reinforces the widely reported role of IFIH1 gene variants on psoriatic disease and other immune mediated diseases.
Keywords
psoriasis; psoriatic arthritis; IFIH1; MDA5; polymorphism; genetic association
Subject
Medicine and Pharmacology, Dermatology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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