Han Zhu, Liu Qingpeng, Sun Chongyi, Li Ying
Department of orthopedic, The 2nd affiliated hospital of Harbin medical university, Harbin, China.
Cell Physiol Biochem. 2012;30(4):898-904. doi: 10.1159/000341467. Epub 2012 Sep 13.
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.
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.
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.
The AGE 82G/S polymorphisms, in interaction with obesity, may determine the susceptibility of OA in Chinese population.
晚期糖基化终末产物受体(RAGE)已被报道与骨关节炎(OA)相关,然而,RAGE基因变异在OA中的作用仍不清楚。
共招募了233例原发性膝关节OA患者和255名健康志愿者。对三个RAGE基因多态性,即Gly82Ser(rs2070600)、-374T/A(rs1800624)和429T/C(rs1800625)进行基因分型。
在所有三个RAGE基因多态性中,只有82G/S多态性的基因型分布和等位基因频率在膝关节OA患者和对照组之间有显著差异。膝关节OA患者中82G/S的SS基因型和S等位基因的存在显著高于对照组(分别为34.76%对19.61%,趋势P =0.004;57.64%对48.59%,趋势P<0.001)。多因素逻辑回归分析显示,与AA基因型相比,SS基因型患膝关节OA的风险显著增加(OR=1.984,95%CI:1.238 - 3.181;P =0.004)。携带S等位基因的校正OR显著高于携带G等位基因(OR=1.440,95%CI:1.137 - 1.8231,P=0.002)。此外,观察到82G/S多态性与肥胖之间存在显著的相乘交互作用(P交互作用=0.028)。以非肥胖的82GG基因型为参照,非肥胖SS携带者患OA的OR为2.537(95%CI 1.241 - 5.189,P=0.001)。值得注意的是,肥胖GS携带者的OR为2.304(95%CI:1.218 - 4.357,P=0.009),肥胖SS携带者的OR为3.392(95%CI:1.672 - 6.885,P=0.001)。-374T/A和-429T/C与肥胖和吸烟状态未显示出正性交互作用。
AGE 82G/S多态性与肥胖相互作用,可能决定中国人群中OA的易感性。