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/m2 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 F2α (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 F2α 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.
Bibliographical noteFunding Information:
We sincerely thank research subjects who participated in the studies described in this report. We also acknowledge financial support from National Research Laboratory project 2005-01572, Ministry of Science & Technology, Korea Science & Engineering Foundation (R01-2003-0000-11709-0), Korea Health 21 R&D Projects, Ministry of Health and Welfare (A000385, A020593), and Korean Academic Foundation (R2004). Brain Korea 21 Project, Yonsei University College of Human Ecology, Brain Korea 21 Project for Medical Science, Yonsei University.
All Science Journal Classification (ASJC) codes
- Endocrinology, Diabetes and Metabolism