Department of Orthopedics, Zibo Central Hospital, Zibo, China.
Department of Orthopedics, Chengdu First People's Hospital, Chengdu, China.
Genet Test Mol Biomarkers. 2021 Feb;25(2):102-110. doi: 10.1089/gtmb.2020.0208.
To study the association of the expression levels of long noncoding RNA Taurine-upregulated gene 1 (lncRNA TUG1) and TUG1 polymorphisms with knee osteoarthritis (KOA). A total of 255 KOA patients and 255 controls from May 2017 to December 2019 were selected for the study. Sanger sequencing was conducted to detect the genotypes of the TUG1 rs5749201, rs7284767, and rs886471 loci in all study subjects. Unconditional logistic regression analysis was used to calculate odds ratios and 95% confidence intervals, and the associations between the rs574901, rs7284767 and rs886471 loci and KOA risk were analyzed. Multifactor dimensionality reduction was used to analyze the interactions among alleles at the three loci examined. Quantitative real-time polymerase chain reaction was used to evaluate the expression levels of lncRNA in plasma. A total of 255 KOA patients and 255 control subjects completed the study. After adjusting for the factors of gender, age, body mass index, smoking history, drinking history, and family history, we found that the carriers of the A allele of the TUG1 rs5749201 locus were 1.36 times more likely to develop KOA than the carriers of the T allele (95% confidence interval [CI] = 1.05-1.75, = 0.02); the G allele of the rs7284767 locus was a protective factor for KOA (odds ratio [OR] = 0.71, 95% CI = 0.54-0.92, = 0.01); and the allelic variation at rs886471 G > T led to an increased risk of KOA by 2.34 times (95% CI = 1.53-3.57, < 0.01). We also found that the GAG haplotype for the three loci was significantly associated with the increased risk of KOA (OR = 2.77, 95% CI = 1.67-4.57, < 0.01). There was no correlation found between the TUG1 rs886471, rs5749201, and rs7284767 single nucleotide polymorphisms loci and the severity of KOA. The allelic variation at TUG1 rs5749201 T > A, rs886471 T > G were associated with decreased levels of lncRNA in the plasma of the subjects, while the allelic variation at rs7284767 A > G was associated with increased levels of lncRNA in plasma ( = 0.01, < 0.01, < 0.01). Plasma lncRNA levels and loci at the rs5749201, rs7284767, and rs886471 loci are associated with KOA risk.
研究长链非编码 RNA 牛磺酸上调基因 1（lncRNA TUG1）表达水平与 TUG1 多态性与膝骨关节炎（KOA）的关联。 本研究选取了 2017 年 5 月至 2019 年 12 月的 255 例 KOA 患者和 255 例对照者。对所有研究对象进行 Sanger 测序，以检测 TUG1 rs5749201、rs7284767 和 rs886471 位点的基因型。采用非条件逻辑回归分析计算比值比和 95%置信区间，并分析 rs574901、rs7284767 和 rs886471 位点与 KOA 风险的关系。多因素维度缩减分析了三个被检测位点等位基因之间的相互作用。采用实时定量聚合酶链反应评估血浆中 lncRNA 的表达水平。 共有 255 例 KOA 患者和 255 例对照者完成了研究。在调整性别、年龄、体重指数、吸烟史、饮酒史和家族史等因素后，我们发现 TUG1 rs5749201 位点 A 等位基因携带者患 KOA 的风险是 T 等位基因携带者的 1.36 倍（95%置信区间[CI]：1.05-1.75，=0.02）；rs7284767 位点 G 等位基因是 KOA 的保护因素（比值比[OR]：0.71，95%CI：0.54-0.92，=0.01）；rs886471 位点 G > T 等位基因变异使 KOA 的风险增加 2.34 倍（95%CI：1.53-3.57，<0.01）。我们还发现三个位点的 GAG 单倍型与 KOA 风险增加显著相关（OR：2.77，95%CI：1.67-4.57，<0.01）。TUG1 rs886471、rs5749201 和 rs7284767 单核苷酸多态性位点与 KOA 严重程度无相关性。TUG1 rs5749201 T > A、rs886471 T > G 等位基因变异与受试者血浆中 lncRNA 水平降低相关，而 rs7284767 位点 A > G 等位基因变异与血浆中 lncRNA 水平升高相关（=0.01，<0.01，<0.01）。血浆 lncRNA 水平和 rs5749201、rs7284767 和 rs886471 位点与 KOA 风险相关。
