The potential impact of polymorphisms in METTL3 gene on knee osteoarthritis susceptibility

Abstract

Objective: This study was aimed to explore the correlation between METTL3 polymorphisms and susceptibility to knee osteoarthritis (KOA).

Methods: The relationship of five single nucleotide polymorphisms (SNPs) in the METTL3 gene with the susceptibility of KOA was analyzed through multinomial logistic regression analysis in this a case-control study. Genotyping was performed on 228 KOA patients and 252 unaffected individuals from South China based on the TaqMan method. The MDR software (version 3.0.2) was utilized for the analysis of SNP interactions.

Results: Out of the five SNPs examined, the T > G change in the METTL3 gene at the rs1061026 locus increased the risk of KOA, while rs1139130 A > G and rs1263802 C > T variants were found to be linked with a reduced risk of developing KOA with statistical significance. The rs1061027 A > C and rs1263801 C > G variants did not show significant association (p＞0.05). The rs1061026 TG/GG genotype showed a significant correlation with an increased risk of KOA in the following subgroups: the males, individuals with a BMI ranging from 24 to 28, smokers, those who were not engaged in physical exercise (PE), patients who had experienced KOA symptoms for eight years or longer, and those without a family history of the disease or reported swelling. On the other hand, the rs1139130 AG/GG genotype demonstrated a protective effect against KOA among the females, individuals with a BMI greater than or equal to 24, a unilateral KOA, or a KOA duration of 8 years or less, non-smokers, non-alcohol drinkers, those who were not engaged in PE, and those who had no injury or family history, or no experience of knee swelling. Additionally, it was observed that the rs1263802 CT/TT genotypes showed a protective effect among patients without a history of injury. Furthermore, individuals with the haplotypes GAT, GGC, TAT, and TGC were found to have a significantly lower susceptibility to KOA compared to the reference haplotype TAC.

Conclusions: The METTL3 gene variant rs1061026 could increase the risk of KOA, whereas the variants of rs1139130 as well as rs1263802 might exert a protective effect against KOA. These variants could potentially function as susceptibility markers for KOA among the population from South China.

Keywords: Knee osteoarthritis; METTL3; Polymorphism; Susceptibility.

Fig. 1

Functional prediction for the polymorphisms of METTL3. (A) Prediction of miRNA binding sites for rs1061026 and rs1061027; (B) Prediction of protein binding sites for rs1263801; (C) Prediction of protein binding sites for rs1263802.

Fig. 2

Interaction map for the risk of knee osteoarthritis. The interaction model describes the percentage of the entropy (information gain) explained by each factor or 2-way interaction. Positive entropy (plotted in red) indicates the interaction, which can be interpreted as a synergistic or nonadditive relationship. In contrast, negative entropy (plotted in yellow-green or green) indicates the independence or additivity (redundancy). (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)