The interaction between obesity and RAGE polymorphisms on the risk of knee osteoarthritis in Chinese population

Background: The receptor for advanced glycation end products (RAGE) has been reported to relate to osteoarthritis (OA), however, the role of RAGE genetic variants in OA remains unknown.

Method: A total of 233 patients with primary knee OA and 255 healthy volunteer were recruited. Three RAGE gene polymorphisms, namely, Gly82Ser (rs2070600). -374T/A (rs1800624) and 429T/C (rs1800625) were genotyped.

Results: Of all three RAGE gene polymorphisms, only the genotype distributions and alleles frequencies of 82G/S polymorphisms significantly differed between knee OA and control subjects. The presence of SS genotype and S allele of 82G/S we significantly higher in knee OA subjects than in controls (34.76% vs. 19.61%, P for trend =0.004; 57.64% vs. 48.59%, P for trend <0.001, respectively). Multivariate logistic regression analysis showed a significantly increased risk for knee OA for the SS genotype compared with the AA genotype (OR= 1.984, 95% CI: 1.238-3.181; P =0.004). The adjusted OR for S allele carriage was significantly higher than G allele carriage (OR=1.440, 95% CI: 1.137-1.8231, P=0.002). Moreover, a significant multiplicative interaction was observed between 82G/S polymorphisms with obesity (Pinteraction=0.028). Taking the non-obese 82GG genotype as references, the OR for OA in non-obese SS carriers was 2.537 (95% CI 1.241-5.189, P=0.001). Notably, the OR in obese GS carriers was 2.304 (95% CI: 1.218-4.357, P=0.009) and in obese SS was 3.392 (95% CI: 1.672-6.885, P=0.001). The -374T/A and -429T/C did not show positive interaction with obesity and smoking status.

Conclusion: The AGE 82G/S polymorphisms, in interaction with obesity, may determine the susceptibility of OA in Chinese population.