Department of Spine, Weifang Hospital of Traditional Chinese Medicine, Weifang, Shandong Province, 261041, China.
Department of Orthopedics, Luoyang Orthopedic Hospital of Henan Province, Luoyang, Henan Province, 471000, China.
J Orthop Surg Res. 2024 Aug 27;19(1):513. doi: 10.1186/s13018-024-05023-0.
Osteoarthritis (OA) is the most prevalent type of arthritis and the main reason for progressive disability in middle-aged and older people. Studies of candidate genes may provide a novel insight and treatment strategy for knee osteoarthritis (KOA). The aim of this study was to investigate the relationship between KOA susceptibility and single-nucleotide polymorphism (SNP) of the ADAMTS-5 gene.
The case group included 188 patients from Luoyang Orthopedic Hospital with clinically and radiographically diagnosed primary KOA, and the control group included 100 age-matched individuals without KOA. Fifteen ADAMTS-5 SNPs were assayed using MALDI-TOF MS. Allelic and haplotypic frequencies were compared between the groups. The relationship between genotype distribution and risk of KOA was analyzed by multivariate logistic regression.
The frequency of A allele in rs2249350 site in the KOA group was significantly lower (odds ratio [OR]: 0.761; 95% confidence interval [95% CI]: 0.612-0.947; P = 0.016), while that of C allele was higher than that in the control group (OR: 1.176; 95% CI: 1.025-1.351; P = 0.016). AA genotype and gene model, especially recessive gene model at rs2249350 locus, negatively correlated with KOA risk after adjustment for sex, body mass index, age, and occupation (AA vs. CC: OR: 0.288; 95% CI: 0.124-0.669; P = 0.004; AA vs. CA + CC: OR: 0.348; 95% CI: 0.162-0.749; P = 0.007). Meanwhile, one protective haplotype, GA (rs229054, rs2249350) (OR: 0.763; 95% CI: 0.614-0.949; P = 0.017), and one high-risk haplotype, GC (rs229054, rs2249350) (OR: 1.259; 95% CI: 1.032-1.537; P = 0.019), were found in this study.
Despite a limited sample size, our study suggests that the rs2249350 polymorphism in the ADAMTS-5 gene is one of the genetic factors influencing the risk of KOA. The A allele and AA genotype of rs2249350 may protect from KOA, whereas C allele and CC genotype increase the risk of KOA. In addition, the GA haplotype (rs229054, rs2249350) might be associated with a decreased risk of KOA, whereas the GC haplotype (rs229054, rs2249350) may be a risk factor for KOA. Additional larger-sized studies in more ethnically diverse populations are needed to confirm these findings.
骨关节炎（OA）是最常见的关节炎类型，也是中老年人进行性残疾的主要原因。候选基因的研究可能为膝骨关节炎（KOA）提供新的见解和治疗策略。本研究旨在探讨 ADAMTS-5 基因单核苷酸多态性（SNP）与 KOA 易感性的关系。
病例组包括来自洛阳正骨医院的 188 例临床和影像学诊断为原发性 KOA 的患者，对照组包括 100 例年龄匹配且无 KOA 的个体。采用基质辅助激光解吸电离飞行时间质谱法（MALDI-TOF MS）检测 15 个 ADAMTS-5 SNPs。比较两组间等位基因和单倍型频率。采用多因素 logistic 回归分析基因型分布与 KOA 风险的关系。
KOA 组 rs2249350 位点 A 等位基因频率明显降低（比值比[OR]：0.761；95%置信区间[95%CI]：0.612-0.947；P=0.016），而 C 等位基因频率高于对照组（OR：1.176；95%CI：1.025-1.351；P=0.016）。经性别、体重指数、年龄和职业校正后，AA 基因型和基因模型，特别是 rs2249350 位点的隐性基因模型，与 KOA 风险呈负相关（AA 与 CC：OR：0.288；95%CI：0.124-0.669；P=0.004；AA 与 CA+CC：OR：0.348；95%CI：0.162-0.749；P=0.007）。同时，发现一个保护性单倍型 GA（rs229054、rs2249350）（OR：0.763；95%CI：0.614-0.949；P=0.017）和一个高危单倍型 GC（rs229054、rs2249350）（OR：1.259；95%CI：1.032-1.537；P=0.019）。
尽管样本量有限，但本研究表明 ADAMTS-5 基因的 rs2249350 多态性是影响 KOA 风险的遗传因素之一。rs2249350 的 A 等位基因和 AA 基因型可能对 KOA 有保护作用，而 C 等位基因和 CC 基因型则增加 KOA 的风险。此外，GA 单倍型（rs229054、rs2249350）可能与 KOA 风险降低相关，而 GC 单倍型（rs229054、rs2249350）可能是 KOA 的危险因素。需要更多在更大样本量且种族多样化的人群中进行的研究来证实这些发现。
