Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, Anhui Province, People's Republic of China.
Department of Sports Injury and Arthroscopic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, Anhui Province, People's Republic of China.
Drug Des Devel Ther. 2021 Dec 21;15:5075-5086. doi: 10.2147/DDDT.S340410. eCollection 2021.
To investigate the correlation of the Val109Asp polymorphism of the omentin-1 gene with the risk and severity of knee osteoarthritis (KOA) in a Chinese Han population.
This study enrolled 383 patients with primary KOA and 460 healthy controls. The genotypes were determined by the detection of single nucleotide polymorphism. To explore the interaction between omentin-1 gene polymorphism and obesity and age, the body mass index (BMI) of 25 kg/m and the age of 55 years old were preset as the cut-off value of stratified analysis. Furthermore, enzyme-linked immunosorbent assay was used to determine the levels of omentin-1, interleukin (IL)-1β, IL-6 in peripheral blood and synovial fluid and the contents of IL-1β, IL-6, metalloproteinase (MMP)-13 and collagen (COL)-II in the supernatant of knee joint cartilage tissue.
The Val109Asp polymorphism of the omentin-1 gene showed no obvious correlation with KOA. Compared with Asp/Asp genotype carriers with BMI <25 kg/m and age <55 years old, Val109 allele carriers with BMI≥25 kg/m and age ≥55 years old had obviously increased risk of KOA (adjusted OR = 1.416, = 0.042; adjusted OR = 1.735, = 0.038, respectively). In the KOA group, only the omentin-1 levels were significantly lower in the plasma and synovial fluid of Ala/Ala genotype carriers than in those of Asp/Asp genotype carriers. Meanwhile, the proportion of patients with moderate-severe K-L Classification, the levels of IL-1β, IL-6 in synovial fluid and the expression levels of IL-1β, IL-6 and MMP-13 in cartilage tissue significantly increased ( < 0.05). By contrast, the expression level of COL-II in cartilage tissue significantly decreased ( < 0.05).
The Val109Asp polymorphism of the omentin-1 gene may not be the primary pathogenic factor of KOA in Chinese. The Val/Val genotype can be regarded as a potential biomarker for the risk of KOA progression.
探讨网膜素-1 基因 Val109Asp 多态性与汉族人群膝骨关节炎(KOA)发病风险及严重程度的相关性。
本研究纳入 383 例原发性 KOA 患者和 460 例健康对照者。采用单核苷酸多态性检测技术确定基因型。为了探讨网膜素-1 基因多态性与肥胖和年龄的相互作用,将体质指数(BMI)为 25kg/m2 和年龄为 55 岁预设为分层分析的截断值。此外,采用酶联免疫吸附试验法测定外周血和滑膜液中网膜素-1、白细胞介素(IL)-1β、IL-6 的水平,以及膝关节软骨组织上清液中 IL-1β、IL-6、基质金属蛋白酶(MMP)-13 和胶原(COL)-II 的含量。
网膜素-1 基因 Val109Asp 多态性与 KOA 无明显相关性。与 BMI<25kg/m2 且年龄<55 岁的 Asp/Asp 基因型携带者相比,BMI≥25kg/m2 且年龄≥55 岁的 Val109 等位基因携带者发生 KOA 的风险明显增加(校正 OR=1.416, =0.042;校正 OR=1.735, =0.038)。在 KOA 组中,仅 Ala/Ala 基因型携带者的血浆和滑膜液中网膜素-1 水平明显低于 Asp/Asp 基因型携带者。同时,中重度 K-L 分级患者的比例、滑膜液中 IL-1β、IL-6 水平以及软骨组织中 IL-1β、IL-6 和 MMP-13 的表达水平均明显升高( < 0.05),而软骨组织中 COL-II 的表达水平明显降低( < 0.05)。
网膜素-1 基因 Val109Asp 多态性可能不是中国人群 KOA 的主要致病因素。Val/Val 基因型可视为 KOA 进展风险的潜在生物标志物。