Department of Oral Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Graduate Program of Dentistry, Pontífice Universidade Católica do Paraná, Curitiba, Paraná, Brazil.
PLoS One. 2020 Mar 4;15(3):e0229245. doi: 10.1371/journal.pone.0229245. eCollection 2020.
Aquaporins (AQPs) are membrane channels that provide for transport of water and other small molecules across the lipid bilayer of cells. Their function is essential for physiologic processes such as cell volume regulation, chondrocyte hypertrophy during appendicular skeletal growth, water reabsorption in the kidney tubules, and water excretion by the salivary glands. The ten AQP isoforms show tissue specificity and are involved in different pathologies and inflammatory diseases. This study addresses the hypothesis that arthritis, periodontitis, and temporomandibular joint disorders (TMDs) can be influenced by variation in the AQP genes at 12q13.12 locus. Salivary samples of 688 individuals were obtained from the Dental Registry and DNA Repository project at the University of Pittsburgh. Ten polymorphisms in four AQP genes (AQP1, 2, 5, and 6) were genotyped and correlated to disease status as reported by patients. Associations were found between the single nucleotide polymorphism (SNP) rs467323 in AQP2 and TMD in both genotypic (p = 0.03) and recessive (p = 0.02) models, and between rs1996315 in AQP6 and periodontitis (p = 0.05). Combined analysis of TMD and periodontitis showed an association with rs3741559 in AQP2 (p = 0.02). When conducting haplotype analysis of rs467323 and rs10875989 in AQP2, the haplotype CT showed an association with the TMD phenotype (p = 0.007). Our results suggest that the aquaporin locus at 12q13.12 may contribute to the pathogenesis of inflammatory conditions such as periodontitis and TMD. Thus, oral and skeletal health are correlated and potential susceptibility screening strategies may be developed.
水通道蛋白（AQP）是一种膜通道，可促进水和其他小分子穿过细胞的脂质双层进行运输。其功能对于生理过程至关重要，如细胞体积调节、四肢骨骼生长期间软骨细胞肥大、肾脏小管中的水重吸收以及唾液腺的水排泄。这十种 AQP 同工型具有组织特异性，参与不同的病理和炎症性疾病。本研究假设关节炎、牙周炎和颞下颌关节紊乱（TMD）可受 12q13.12 位 AQP 基因变异的影响。匹兹堡大学的牙科登记和 DNA 存储库项目获得了 688 名个体的唾液样本。对四个 AQP 基因（AQP1、2、5 和 6）的 10 个多态性进行了基因分型，并根据患者报告的疾病状况进行了相关分析。在 AQP2 的单核苷酸多态性（SNP）rs467323 与 TMD 的基因型（p=0.03）和隐性（p=0.02）模型中发现了关联，在 AQP6 的 rs1996315 与牙周炎之间也发现了关联（p=0.05）。TMD 和牙周炎的联合分析显示，AQP2 的 rs3741559 与两者都有关联（p=0.02）。当对 AQP2 的 rs467323 和 rs10875989 进行单体型分析时，CT 单体型与 TMD 表型相关（p=0.007）。我们的研究结果表明，12q13.12 上的水通道蛋白基因座可能有助于牙周炎和 TMD 等炎症性疾病的发病机制。因此，口腔和骨骼健康相关，可能开发出潜在的易感性筛查策略。
