Putative functional variants of lncRNA identified by RegulomeDB were associated with knee osteoarthritis susceptibility.

Background: Knee osteoarthritis (KOA) is the most common form of chronic degenerative joint disease worldwide. Its incidence has increased in recent years. Aberrant expression profile of lncRNAs in damaged bone and cartilage of KOA patients has been reported recently, indicating its potential contributions in KOA development and a promising target for disease diagnosis and treatment. The aim of this study was to identify the association between genetic variation in lncRNA and KOA.

Methods: We retrieved relevant articles from the PubMed, Medline and Embase databases up to Jul 2017 investigating the association between lncRNA and the risk of osteoarthritis. There are 15 lncRNAs which show connection with osteoarthritis. We selected potential functional polymorphisms identified by RegulomeDB database in these lncRNAs. A case-control study was conducted which contained 278 KOA patients and 289 OA-free controls.

Results: Logistic regression analyses revealed that H19 rs2067051 T allele was significantly associated with decreased risk of KOA after adjusted for age, gender and BMI in recessive genetic model (OR = 0.63, P = 0.03) and additive genetic model (OR = 0.79, P = 0.03). MEG3 rs4378559 T allele was significantly associated with increased risk of KOA in additive genetic model (OR = 1.32, P = 0.04). Heterogeneity tests proved that H19 rs2067051, MEG3 rs4378559 and HOTTIP rs202384's risk effects on KOA were more remarkable for female, BMI ≥ 25 and younger age (age < 60), respectively.

Conclusion: The results indicate that potential functional genetic variation in lncRNA plays an important role in the pathogenesis of KOA.