Department of Hip Injury and Disease, Luoyang Orthopedic Hospital of Henan Province, Luoyang, Henan, China.
Department of Ankle and Disease Injury and Disease, Luoyang Orthopedic Hospital of Henan Province, Luoyang, Henan, China.
Sci Rep. 2018 Jul 6;8(1):10243. doi: 10.1038/s41598-018-28597-2.
Multiple lines of evidence have confirmed the importance of genetic factors for hip osteoarthritis (HOA). Our study aimed to investigate the associations of TLR10 and NFKBIA with respect to the HOA risk in Han Chinese individuals. A total of 1,043 HOA patients and 2,664 controls were recruited. Then, 23 tag single-nucleotide polymorphisms (SNPs) in the TLR10 and NFKBIA genes were selected for genotyping. Genetic association analyses were conducted in both single-marker and haplotype-based ways. Gene by gene, two-way interactions were analysed using a case-only method. Multiple bioinformatics tools were utilised to examine the potential functional significance of the SNPs. Two significant SNPs, rs11096957 (OR = 1.26, P = 1.35 × 10) and rs2273650 (OR = 1.2, P = 1.57 × 10), were significantly associated with HOA risk. Rs11096957 was also associated with the severity of the HOA. Bioinformatics analysis indicated that the allele T of rs2273650 would create new miRNA/SNP target duplexes, which suggests that rs2273650 could alter the NFKBIA expression by affecting the miRNA/SNP target duplexes. Our study identified significant association signals from NFKBIA with HOA for the first time, and it also confirmed the contribution of TLR10 to the HOA risk. These findings would provide clues for identifying individuals at high risk of HOA.
大量证据证实了遗传因素对髋骨关节炎(HOA)的重要性。我们的研究旨在探讨 TLR10 和 NFKBIA 与汉族个体 HOA 风险的相关性。共招募了 1043 名 HOA 患者和 2664 名对照者。然后,选择 TLR10 和 NFKBIA 基因中的 23 个标签单核苷酸多态性(SNP)进行基因分型。采用单体型和单体型两种方法进行遗传关联分析。使用病例仅方法分析基因与基因之间的双向相互作用。利用多种生物信息学工具检查 SNP 的潜在功能意义。两个显著的 SNP,rs11096957(OR=1.26,P=1.35×10)和 rs2273650(OR=1.2,P=1.57×10),与 HOA 风险显著相关。rs11096957 也与 HOA 的严重程度相关。生物信息学分析表明,rs2273650 的等位基因 T 会产生新的 miRNA/SNP 靶双链,这表明 rs2273650 可能通过影响 miRNA/SNP 靶双链来改变 NFKBIA 的表达。我们的研究首次发现 NFKBIA 与 HOA 之间存在显著的关联信号,并证实了 TLR10 对 HOA 风险的贡献。这些发现将为识别 HOA 高危个体提供线索。