Association analysis of juvenile idiopathic arthritis genetic susceptibility factors in Estonian patients.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic condition of childhood. Genetic association studies have revealed several JIA susceptibility loci with the strongest effect size observed in the human leukocyte antigen (HLA) region. Genome-wide association studies have augmented the number of JIA-associated loci, particularly for non-HLA genes. The aim of this study was to identify new associations at non-HLA loci predisposing to the risk of JIA development in Estonian patients. METHODS: We performed genome-wide association analyses in an entire JIA case-control sample (All-JIA) and in a case-control sample for oligoarticular JIA, the most prevalent JIA subtype. The entire cohort was genotyped using the Illumina HumanOmniExpress BeadChip arrays. After imputation, 16,583,468 variants were analyzed in 263 cases and 6956 controls. RESULTS: We demonstrated nominal evidence of association for 12 novel non-HLA loci not previously implicated in JIA predisposition. We replicated known JIA associations in CLEC16A and VCTN1 regions in the oligoarticular JIA sample. The strongest associations in the All-JIA analysis were identified at PRKG1 (P = 2,54 × 10-6), LTBP1 (P = 9,45 × 10-6), and ELMO1 (P = 1,05 × 10-5). In the oligoarticular JIA analysis, the strongest associations were identified at NFIA (P = 5,05 × 10-6), LTBP1 (P = 9,95 × 10-6), MX1 (P = 1,65 × 10-5), and CD200R1 (P = 2,59 × 10-5). CONCLUSION: This study increases the number of known JIA risk loci and provides additional evidence for the existence of overlapping genetic risk loci between JIA and other autoimmune diseases, particularly rheumatoid arthritis. The reported loci are involved in molecular pathways of immunological relevance and likely represent genomic regions that confer susceptibility to JIA in Estonian patients. Key Points • Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease with heterogeneous presentation and genetic predisposition. • Present genome-wide association study for Estonian JIA patients is first of its kind in Northern and Northeastern Europe. • The results of the present study increase the knowledge about JIA risk loci replicating some previously described associations, so adding weight to their relevance and describing novel loci. • The study provides additional evidence for the existence of overlapping genetic risk loci between JIA and other autoimmune diseases, particularly rheumatoid arthritis.

Contemporary management of TMJ involvement in JIA patients and its orofacial consequences.

Juvenile idiopathic arthritis is the most common chronic rheumatic condition during childhood. Temporomandibular joint arthritis is frequently asymptomatic. When it takes place during childhood, it may affect condylar growth; therefore, these children are at risk of unfavorable long-term outcomes from the associated joint damage. The etiology is not completely understood, but it is considered as multifactorial with both genetic and environmental factors involved. The standardized examination and imaging protocols serve important purpose to diagnose temporomandibular joint (TMJ) arthritis not only to establish an early interventional strategy but also to assess craniofacial growth and the progression of signs and symptoms in those patients. Although the treatment of juvenile idiopathic arthritis (JIA) has changed dramatically over the last decades due to new therapeutic options, TMJ arthritis still can develop during the course of the disease. In clinical experience, TMJs appear to respond less well to the standard of care used to treat other joints. More individualized approach to the patient's treatment serves as the main goal of personalized medicine. It could be achieved by adopting new methods of medical imaging such as conebeam computer tomography as well as developing reliable biomarkers which may assist with predicting disease type, course, or severity and predicting response to medication. This article provides an overview of current information on orofacial complications in JIA and its management. Based on information provided in this review, more precise diagnosis, proper tools for recognizing people at risk, and more efficient treatment approaches could be implemented. This may lead to more personalized treatment management strategies of TMJ complications of JIA patients.