IRF7 Gene Variations Confer Susceptibility to Autoimmune Thyroid Diseases and Graves’ Ophthalmopathy

Abstract

The objective of this study was to investigate whether IRF7 polymorphisms are associated with autoimmune thyroid diseases (AITDs). We selected three single nucleotide polymorphisms (SNPs) of IRF7, namely, rs1061501, rs1131665, and rs1061502 for genotyping using PCR-based ligase detection reaction (LDR) method in a total of 1659 participants (592 with Graves' disease, 297 with Hashimoto's thyroiditis, and 770 healthy controls). Gene-disease and genotype-clinical phenotype associations were evaluated for the three SNPs. Our results showed that the AG genotype and the minor allele G frequency of rs1131665 and rs1061502 in AITD patients were both higher than those of the controls (rs1131665: AG genotype: P = 0.017, OR = 1.968; allele G: P = 0.018, OR = 1.946; rs1061502: AG genotype: P = 0.029, OR = 1.866; allele G: P = 0.031, OR = 1.847). Subgroup analysis also showed that the AG genotype and the minor allele G frequency of rs1131665 and rs1061502 in Graves' disease patients were both higher than those of the controls (rs1131665: AG genotype: P = 0.015, OR = 2.074; allele G: P = 0.016, OR = 2.048; rs1061502: AG genotype: P = 0.034, OR = 1.919; allele G: P = 0.035, OR = 1.898). Furthermore, the allele G frequency of rs1061501 was associated with Graves' ophthalmopathy (P = 0.035, OR = 1.396). No significant difference in IRF7 polymorphisms was found between Hashimoto's thyroiditis patients and controls. Our study has revealed for the first time that IRF7 is a susceptibility gene for AITD, especially for Graves' disease and Graves' ophthalmopathy.

Anti‐N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis is associated with IRF7, BANK1 and TBX21 polymorphisms in two populations

“…The most important finding of the present study was the strong association of anti‐NMDAR encephalitis with IRF7 rs1131665 (T > C), with the minor C allele associated with a more than threefold risk of disease in both case–control sets. In line with this finding, the minor C allele of rs1131665 was also associated with an increased risk of autoimmune thyroid diseases and Graves' ophthalmopathy [10]. However, the association of IRF7 rs1131665 with systemic lupus erythematosus (SLE) and systemic sclerosis was in another direction, where the major T allele was associated with risk of SLE and the presence of anti‐centromere autoantibodies in the patients with systemic sclerosis [11,12].…”

Evaluation of the peripheral blood T and B cell subsets and IRF‐7 variants in adult patients with severe influenza virus infection

“…The variants were investigated in the literature and databases (gnomAD, ExAC, 1000Genomes, dbSNP data bases), and rs1061502 / K179E was found to be associated with systemic lupus erythematosus (SLE) and Graves' disease and Graves' ophthalmopathy, however, our patients had none of them. 22 , 23 …”

IRF7: role and regulation in immunity and autoimmunity

“…IRF7 is a susceptibility gene for AITD, especially for GD and Graves’ ophthalmopathy. In a Chinese Han cohort, the IRF7 SNPs rs1131665 and rs1061502 were associated with increased susceptibility to GD, while rs1061501 was correlated with ophthalmopathy in GD patients ( 177 ). The function and mechanism of IRF7 in AITDs have not been clarified.…”