Institute of Dentistry, University of Tartu, Tartu, Estonia.
Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
J Oral Rehabil. 2024 Nov;51(11):2445-2451. doi: 10.1111/joor.13834. Epub 2024 Aug 27.
Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic condition of childhood. Temporomandibular joint (TMJ) is among the most commonly affected joints in JIA patients. When JIA involves the TMJ, it may affect condylar growth in the joint; therefore, JIA patients are at risk of unfavourable long-term outcomes from associated joint damage. If undetected, TMJ involvement can lead to various functional disabilities such as reduced mandibular mobility and disorders of the mastication muscles. Limitations in sagittal and vertical mandibular growth can result in micrognathia and anterior open bite with aesthetic and functional restrictions.
Genetic factors may play a role in determining which individuals are more prone to develop TMJ disorders or in predicting the severity of the disease process. Therefore, we applied a GWAS approach to identify loci associated with TMJ involvement in a sample of Estonian patients with JIA. Our aim was to address the potential role of genetic susceptibility factors in TMJ-JIA, a condition not previously studied in this context.
The case group consisted of 55 JIA patients with TMJ involvement and 208 patients without TMJ involvement comprised the control group. The entire cohort was genotyped using the Illumina HumanOmniExpress BeadChip arrays. Imputation was performed using a nationwide reference panel obtained of 2240 individuals whose data were obtained from the Estonian Biobank.
We identified six loci as being associated with the risk of TMJ-JIA in Estonian JIA patients. The strongest associations were identified at CD6 rs3019551 (P = 3.80 × 10), SLC26A8/MAPK14 rs9470191 (P = 6.15 × 10), NLRP3 rs2056795 (P = 8.91 × 10) and MAP2K4 rs7225328 (P = 1.64 × 10).
This study provides first insights into the risk-associated loci between JIA and its manifestation in the TMJ. The reported loci are involved in molecular pathways of immunological relevance and likely represent genomic regions that render the TMJ susceptible to involvement by JIA in Estonian patients.
幼年特发性关节炎（JIA）是儿童中最常见的慢性风湿性疾病。颞下颌关节（TMJ）是 JIA 患者最常受影响的关节之一。当 JIA 累及 TMJ 时，它可能会影响关节中的髁突生长；因此，JIA 患者存在因关节损伤而导致不良长期后果的风险。如果未被发现，TMJ 受累可导致各种功能障碍，例如下颌运动受限和咀嚼肌紊乱。下颌矢状和垂直生长受限可导致小颌畸形和前牙开颌，伴有美学和功能限制。
遗传因素可能在决定哪些个体更容易发生 TMJ 疾病或预测疾病过程的严重程度方面发挥作用。因此，我们应用 GWAS 方法在爱沙尼亚 JIA 患者样本中鉴定与 TMJ 受累相关的基因座。我们的目的是探讨 TMJ-JIA 中遗传易感性因素的潜在作用，这是在该背景下尚未研究过的一种情况。
病例组由 55 名 TMJ 受累的 JIA 患者组成，对照组由 208 名无 TMJ 受累的患者组成。整个队列均使用 Illumina HumanOmniExpress BeadChip 阵列进行基因分型。使用从爱沙尼亚生物库获得的包含 2240 人的全国性参考面板进行 imputation。
我们确定了六个基因座与爱沙尼亚 JIA 患者的 TMJ-JIA 风险相关。在 CD6 rs3019551（P = 3.80 × 10）、SLC26A8/MAPK14 rs9470191（P = 6.15 × 10）、NLRP3 rs2056795（P = 8.91 × 10）和 MAP2K4 rs7225328（P = 1.64 × 10）处发现最强的关联。
本研究首次提供了 JIA 及其在 TMJ 中表现之间与风险相关基因座的见解。报道的基因座参与免疫相关的分子途径，可能代表使 TMJ 易受爱沙尼亚 JIA 患者受累的基因组区域。
