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.
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 alpha (TNF-alpha) (P = .033), serum C-reactive protein (CRP) (P= .002), and urinary excretion of 8-epi-prostaglandin F(2alpha) (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-alpha, serum CRP, and 8-epi-prostaglandin F(2alpha) 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-alpha 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.
Jang
Yangsoo
Y
Division of Cardiology, Cardiovascular Genome Center, Yonsei Medical Institute, Yonsei University, Seoul, South Korea.
Kim
Ji Young
JY
Kang
Seok-Min
SM
Kim
Jung-Sun
JS
Chae
Jey Sook
JS
Kim
Oh Yoen
OY
Koh
Soo Jeong
SJ
Lee
Hyun Chul
HC
Ahn
Chul Woo
CW
Song
Young Duk
YD
Lee
Jong Ho
JH
D020121:5' Untranslated Regions / Q000235:genetics; D052242:Adiponectin / Q000097:blood; D000328:Adult; D000368:Aged; D000886:Anthropometry; D015415:Biomarkers; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D002097:C-Reactive Protein / Q000378:metabolism; D015237:Dinoprost / Q000652:urine; D005091:Exons / Q000235:genetics; D005260:Female; D005838:Genotype; D017127:Glycation End Products, Advanced / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000097:blood*; D007328:Insulin / Q000097:blood; D007723:Korea; D008054:Lipid Peroxides / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood* / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D020121:5' Untranslated Regions; D052242:Adiponectin; D015415:Biomarkers; D001786:Blood Glucose; D017127:Glycation End Products, Advanced; D007328:Insulin; D008054:Lipid Peroxides; D008055:Lipids; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D015237:Dinoprost