Association between IL1B rs16944 polymorphism and the risk of idiopathic inflammatory myopathies

Irene Mendoza¹Ignacio Garcia-De La Torre^2,3*Lilia Andrade-Ortega^4,5Monica Vázquez-Del Mercado^6,7Karina Lamadrid-Gamez³Daniel Pérez-Covarrubias⁸

• ¹Instituto Politecnico Nacional, Mexico City, Mexico
• ²Immunology and Rheumatology, University of Guadalajara, Guadalajara, Jalisco, Mexico
• ³Hospital General de Occidente, Guadalajara, Mexico
• ⁴Centro Medico Nacional 20 de Noviembre, Mexico City, Mexico
• ⁵Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Mexico City, Mexico
• ⁶Universidad de Guadalajara, Guadalajara, Mexico
• ⁷Hospital Civil de Guadalajara Dr. Juan I Menchaca, Guadalajara, Mexico
• ⁸Centro de Estudios de Investigacion Basica y Clinica, Guadalajara, Mexico

Introduction: Idiopathic inflammatory myopathies (IIMs) are autoimmune, systemic diseases that affect skeletal muscles. The causes are not fully understood. IIMs presents with proximal weakness, elevated muscle enzymes (primarily creatine phosphokinase, or CPK), and multiorgan involvement, often pulmonary. Muscle tissue shows leukocyte infiltration, and specific autoantibodies are present. We aimed to investigate the possible association between the IL1B rs16944 polymorphism and risk of developing IIMs. Methods: DNA was extracted from blood samples collected from 57 patients with IIMs and 50 healthy controls. The IL1B rs16944 polymorphism was analyzed. Myositis-specific autoantibodies (MSAs), myositis-associated autoantibodies (MAAs) and antinuclear antibodies (ANAs) were determined. The IIMs subtypes in our patients were dermatomyositis, polymyositis, amyopathic dermatomyositis, juvenile dermatomyositis, cancer-associated myositis, scleromyositis, and antisynthetase syndrome. The most frequent were dermatomyositis (47.4%), polymyositis (22.8%), and cancer-associated myositis (17.5%). Regarding ANAs, the three most frequent patterns in patients were: AC-4 (Nuclear fine speckled, 40%); AC-21 (Cytoplasmic reticular/AMA, 10%); and AC-19 (Cytoplasmic dense fine speckled, 8.6%), while 15.7% were negative. The most frequent MSAs in IIMs were Anti-SAE1 (12.5%), Anti-MDA5 (10.7) and Anti-TIF1g (10.7%). The most common MAAs were: Anti-Ro52 (30.4%), Anti-Ku (14.3%), and Anti-PM100 (5.4%). Analysis of the IL1B polymorphism rs16944 revealed a significant association with susceptibility to idiopathic inflammatory myopathies, in the codominant model (CC vs CT, OR= 4.6136, 95% CI: 1.83-11.65, p= 0.0012), dominant model (OR= 3.432, 95% CI: 1.47-7.98, p= 0.0044) and overdominant model (OR= 3.587, 95% CI: 1.58-7.92, p=0.0021). In female patients, significant differences were observed between cases and healthy controls in the codominant (CC vs. CT), dominant, and overdominant genetic models (p= 0.0015, 0.0038, and OR= 4.5043, 95% CI: 1.59-12.68, p= 0.0044, respectively). A significant association could be observed with dermatomyositis (DM), polymyositis (PM), DM+PM, Juvenile DM, Amyopayhic DM, Antisynthetase syndrome (ASyS), and Cancer-associated myositis (CAM). Enzyme levels of creatine phosphokinase (CPK), presented significant differences in our idiopathic inflammatory myopathy (IIMs) patients. The rs16944 polymorphism is significantly associated with various clinicopathological characteristics. Conclusion: This study has, for the first time, revealed an association between the IL1B rs16944 CC (codominant and dominant models) and CCTT (overdominant) genotypes and the IIMs phenotype .