Association of the Gly82Ser polymorphism in the receptor for advanced glycation end products ( RAGE) gene with circulating levels of soluble RAGE and inflammatory markers in nondiabetic and nonobese Koreans

Abstract

We investigated the association between the Gly82Ser (G82S) polymorphism in the receptor for advanced glycation end products ( RAGE) gene and circulating levels of soluble RAGE (sRAGE), advanced glycation end products (AGEs), and inflammatory markers in nondiabetic/nonobese Koreans. A total of 1096 men and 580 women aged 30 to 69 years and with body mass index of 18.5 to 29.9 kg/m 2 were recruited. Anthropometrics, lipid profiles, glucose, insulin, insulin resistance (IR), RAGE G82S polymorphism, sRAGE, AGEs, and inflammatory markers were measured. There was a significant association between G82S genotypes and plasma sRAGE concentrations ( P < .001). sRAGE concentrations were significantly higher in subjects with the G/G genotype (1038 ± 33 pg/mL) than in those with the G/S (809 ± 19 pg/mL) or the S/S (428 ± 43 pg/mL) genotype. Furthermore, the G82S genotypes in the RAGE gene were associated with serum AGE ( P = .033), homeostasis model assessment for insulin resistance (HOMA-IR) ( P < .001), plasma tumor necrosis factor α (TNF- α) ( P = .033), serum C-reactive protein (CRP) ( P= .002), and urinary excretion of 8- epi-prostaglandin F 2 α ( P = .028) after adjusting for sex, age, body mass index, cigarette smoking, and alcohol drinking. Subjects with the S/S genotype showed higher levels of serum AGE, HOMA-IR, plasma TNF- α, serum CRP, and 8- epi-prostaglandin F 2 α than those with the G/G or G/S combination. The sRAGE levels showed a negative relation with high-sensitivity CRP ( r = −0.250; P < .001). The AGE concentrations showed a positive relation with TNF- α levels ( r = 0.398; P < .001). Subjects with homozygosity for the minor S allele (S/S) of the G82S polymorphism had higher risk factors for cardiovascular disease, such as low sRAGE levels, inflammation, oxidative stress, and IR, compared with those bearing at least one G allele.