Genetic Susceptibility to Antisynthetase Syndrome Associated With Single-Nucleotide Variants in the IL1B Gene That Lead Variation in IL-1β Serum Levels

IL1B 基因单核苷酸变异导致 IL-1β 血清水平变化,与抗合成酶综合征的遗传易感性有关

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作者:Marco Antonio Ponce-Gallegos, Espiridión Ramos-Martínez, Adriana García-Carmona, Mayra Mejía, Karol J Nava-Quiroz, Gloria Pérez-Rubio, Enrique Ambrocio-Ortiz, Montserrat I González-Pérez, Ivette Buendía-Roldán, Jorge Rojas-Serrano, Ramcés Falfán-Valencia

Abstract

The antisynthetase syndrome (ASSD) is an autoimmune disorder characterized by myositis, arthritis, mechanic's hands, fever, Raynaud phenomenon, and interstitial lung disease (ILD). We aimed to evaluate single-nucleotide polymorphisms in the interleukin 1B (IL1B) gene and their association between ILD with antisynthetase autoantibodies, as well as IL-1β serum levels. The most frequent antisynthetase autoantibody was anti-Jo1. The most frequent tomographic pattern was non-specific interstitial pneumonia, whereas in the anti-Jo1 subjects, it was organized pneumonia. Anti-Jo1 patients tend to have more significant arthritis, and Raynaud phenomenon have higher levels of creatinine phosphokinase. In the IL1B gene, the GG genotype and G allele of rs1143634 [odds ratio (OR) = 2.21 and OR = 2.60, respectively, p < 0.05] are associated with an increased risk, as well as with the dominant and recessive models (p < 0.05). This finding is maintained after logistic regression analysis adjusting for potential confounding variables (p < 0.05). Subjects with the rs16944/AG heterozygous genotype had higher serum levels of IL-1β compared to homozygous (p < 0.05). In conclusion, rs1143634 is associated with a higher risk of ASSD. Also, the GA genotype is associated with higher levels of IL-1β in ASSD patients.

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