Mixed connective tissue disease (
MCTD) is a rare complex
autoimmune disease in which
autoantigens are recognized by endosomal TLRs. Their activation induces a higher secretion of the
type I interferons, IFN-γ and the up-regulation of the INF-inducible genes. The present study aimed to investigate whether SNPs that are located in the IFN-A, IFN-B, and IFN-G genes are associated with
MCTD. 145
MCTD patients and 281 healthy subjects were examined for IFN-A, IFN-B, and IFN-G genetic variants by TaqMan SNP genotyping assay. ELISA determined IFN-α/-β/-γ serum levels. Among the seven tested SNPs, four polymorphisms: IFN-A rs10757212, IFN-A rs3758236, IFN-G rs2069705, IFN-G rs2069718, as well as INF-G rs1861493A/rs2069705A/rs2069718G haplotype were significantly associated with a predisposition for
MCTD. Raynaud's phenomenon, erosive
arthritis, swollen hands and fingers, and sclerodactyly were significantly more frequently observed in
MCTD patients with IFN-G rs2069718 G allele than in patients with IFN-G rs2069718 A allele. We also found that anti-U1-A
autoantibodies most frequently occurred in
MCTD patients with rs2069718 GA genotype, while the IFN-G rs2069705 AG and rs2069718 GA genotypes might be a marker of anti-Ro60 presence in
MCTD patients. Our results indicate that IFN-G genetic variants may be potential genetic
biomarkers for
MCTD susceptibility and severity.