G allele at RAGE SNP82 is associated with proinflammatory markers in obese subjects

Abstract

Obesity is closely associated with low-grade inflammation. The Gly82Ser (G82S) polymorphism in the receptor for the advanced glycation end products (RAGE) gene related to RAGE expression is also involved in inflammatory response. We examined the association between RAGEG82S and obesity on soluble RAGE (sRAGE) and inflammatory markers in Korean men. The following were measured: anthropometric and biochemical parameters, RAGEG82S polymorphism, sRAGE, advanced glycation end products (AGEs), and inflammatory markers in men (n = 1252; range, 30-70 years; body mass index [BMI], > or =18.5 kg/m(2)). Allele frequencies satisfied Hardy-Weinberg Equilibrium (G/G: 72.2%, G/S: 25.5%, S/S: 2.3%). RAGEG82S (beta-coefficient = -0.384, P < .001) and BMI (beta-coefficient = -0.168, P = .001) were major factors affecting sRAGE concentrations. In all subjects, those with 'S/S' homozygotes showed the lowest levels of sRAGE (G/G: 1036.3 +/- 40.3, G/S: 807.0 +/- 49.6, S/S: 443.0 +/- 47.8 pg/mL) before (P < .001) and after adjusted for age, BMI, cigarette smoking, and alcohol drinking (P < .001). When subdivided according to BMI of 25 kg/m(2) (Asian Pacific guideline), obese subjects (BMI > or =25 kg/m(2)) had significantly lower levels of sRAGE (831.7 +/- 36.7 vs 1022.7 +/- 47.8 pg/mL, P = .009) and higher levels of high sensitivity C-reactive protein (hs-CRP) (1.10 +/- 0.07 vs 0.72 +/- 0.05 mg/dL, P < .001) compared with nonobese subjects (BMI <25 kg/m(2)). Particularly in obese subjects, S/S carriers showed significantly higher concentrations of AGEs (P = .012) and hs-CRP (P = .006) than G allele carriers, whereas nonobese people had no significant RAGEG82S-related differences in AGEs (P = .743) and hs-CRP (P = .436). In conclusion, G allele at RAGEG82S may be more associated with inflammatory markers under obese status than nonobese conditions. In this case, it may help to suggest proper dietary modification for controlling obesity to people with genetic variants.