Objective: 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). Materials and Methods: 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 TUG1 rs574901, rs7284767 and rs886471 loci and KOA risk were analyzed. Multifactor dimensionality reduction was used to analyze the interactions among alleles at the three TUG1 loci examined. Quantitative real-time polymerase chain reaction was used to evaluate the expression levels of TUG1 lncRNA in plasma. Results: 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, p = 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, p = 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, p < 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, p < 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 TUG1 lncRNA in the plasma of the subjects, while the allelic variation at rs7284767 A > G was associated with increased levels of TUG1 lncRNA in plasma (p = 0.01, p < 0.01, p < 0.01). Conclusion: Plasma TUG1 lncRNA levels and loci at the TUG1 rs5749201, rs7284767, and rs886471 loci are associated with KOA risk.
Keywords: Taurine-upregulated gene 1; gene polymorphism; knee osteoarthritis; long noncoding RNA.