Relationship among sRAGE, AGE and CRP according to RAGE Gly82Ser and obesity status in Korean men

Abstract

[한글]저자는 AGE-RAGE binding이 강화되는 RAGE Gly82Ser genotype 및 obesity 같은 상황에서 sRAGE, AGE, CRP 의 혈중 농도의 변화를 측정하여 이들간의 상호 관계를 알아보고자 하였다. 30-70세 사이의 BMI≥18.5kg/m2 를 가진 총 1096명의 남성 이 실험에 모집되었고, anthropometrics, lipid profiles, glucose, RAGE G82S polymorphism, sRAGE, AGEs, inflammatory markers (CRP and IL-6) 등을 측정하였다. soluble RAGE는 RAGE Gly82Ser genotype에 의해 영향을 받았으며 82 S/S genotype 군에서 현저하게 낮았다 (G/G: 1036.3±40.3 pg/ml and G/S: 807.0±49.6 pg/ml, S/S: 443.0±47.8 pg/ml, p<0.001). Stepwise analysis를 통해 RAGE Gly82Ser genotype과 BMI가 sRAGE에 영향을 주는 것으로 나타났다 (standardized β-coefficient = -0.384, p<0.001, standardized β-coefficient = -0.168, p=0.001). sRAGE는 obese group에서 현저하게 낮았으며 (S/S:439.5±57.7 pg/ml G/G:917.5±45.7 pg/ml G/S (768.8±56.1 pg/ml) (p<0.001)), Obesity가 동반된 82 S/S geotype 군에서 soluble RAGE가 낮았을 뿐더러 CRP의 상승 및 AGE의 상승도 관찰할 수 있었다 (p=0.012 and p=0.006, respectively). sRAGE는 AGE-RAGE binding affinity가 강화되는 RAGE Gly82Ser genotype과 비만에 의해 영향을 받는 것으로 사료 되며 82 S/S genotype군에서 비만과 같이 inflammation이 증가되어 지는 상황이 동반되었을 때 soluble RAGE의 감소와 더불어 AGE와 CRP의 상승하게 되는 것으로 보인다.

[영문]We studied the relationship among souble receptor for advanced glycation end products (sRAGE), AGE and inflammatory markers according to RAGE Gly82Ser gene polymorphism and obesity, a low-grade inflammatory state. We measured circulating concentrations of sRAGE, AGE and inflammatory markers (CRP and IL-6) in a group of Korean men. A total of 1096 men aged 30~70 years with body mass index≥18.5kg/m2 were recruited. Anthropometric parameters, lipid profiles, glucose, RAGE G82S polymorphism, sRAGE, AGEs, and inflammatory markers (CRP and IL-6) were measured. sRAGE concentrations were lowest in those with homozygous mutation, ‘S/S’ (G/G: 1036.3±40.3, G/S: 807.0±49.6 and S/S: 443.0±47.8pg/ml, p<0.001), which maintained after adjusted for age, BMI, cigarette smoking and alcohol drinking (p<0.001). Stepwise regression showed that RAGE Gly82Ser genotype (β-coefficient=-0.384, p<0.001) and BMI (β-coefficient=-0.168, p=0.001) were major influencing factors on sRAGE concentration. Obese subjects (BMI≥25kg/m2) had significantly lower levels of sRAGE (831.7±36.7pg/ml) than non-obese subjects (1022.7±47.8pg/ml) (p=0.009). In Obese subjects, the ‘S/S’ group had lower concentrations of sRAGE (439.5±57.7pg/ml) than the G/G (917.5±45.7 pg/ml) or the G/S group (768.8±56.1pg/ml) (p<0.001). On the other hand, the obese subject with the S/S genotype showed higher concentrations of AGE and CRP comparing with those with the G/G or G/S genotype (p=0.012 and p=0.006, respectively). In conclusion, sRAGE is influenced by RAGE G82S polymorphism and obesity status as a result of enhanced AGE-RAGE binding affinity. Inflammatory condition such as obesity not only decreases sRAGE levels but also increases AGE and CRP levels particularly in subjects with RAGE 82 S/S genotype.