Association between interleukin-6 receptor gene variations and atherosclerotic lipid profiles among young adolescents in Taiwan

Abstract

BackgroundTo analyze the potential genetic associations between four polymorphisms of interleukin-6 receptor (IL-6R) gene and atherosclerotic lipid profiles among young adolescents in Taiwan.MethodsUsing data from the Taipei Children Heart Study-II - a cross-sectional survey in 2003. After multi-stage sampling, we selected 418 boys and 441 girls with an average age of 13.1 years. We genotyped the subjects for four IL-6R gene polymorphisms (rs4845617 G/A, rs4845623 A/G, rs8192284 A/C, and rs2229238 C/T) using a TaqMan 5' nuclease assay. Lipid profiles, including total cholesterol (CHOL), triglycerides (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C) were measured using standard methods. We also calculated CHOL/HDL-C ratio, LDL-C/HDL-C ratio, and TG/HDL-C ratio as atherosclerotic indexes.ResultsIL-6R rs8192284 A/C and rs2229238 C/T variants showed strong associations with high TG (additive model, OR = 1.58, 95%CI: 1.05-2.37; OR = 1.55, 95%CI: 1.04-2.29, respectively), low HDL-C (additive model, OR = 1.57, 95%CI: 1.03-2.39; OR = 1.68, 95%CI: 1.12-2.52, respectively), and high CHOL/HDL-C (additive model, OR = 1.68, 95%CI: 1.08-2.61, OR = 1.82, 95%CI: 1.18-2.79, respectively) in girls. We inferred five common haplotypes using rs4845617 G/A, rs4845623 A/G, and rs2229238 C/T (GAC, GAT, GGC, AAC, and AAT). In girls, the AAT haplotype was associated with a significant risk of high TG, low HDL-C, high CHOL/HDL-C, and abnormal lipid levels (high TG or low HDL-C) when compared with the GAC haplotype (OR range = 3.08-4.40, all p < 0.05).ConclusionThe IL-6R rs8192284 A/C and rs2229238 C/T variants are associated with dyslipidemia in girls, but not in boys. The AAT haplotype of the IL-6R gene (rs4845617 G/A, rs4845623 A/G, and rs2229238 C/T) may play an important role in the pathogenesis of dyslipidemia and atherosclerosis in girls.

Association of genetic variants with dyslipidemia

“…In addition, IL6 has been reported to inhibit lipoprotein lipase activity and stimulate lipolysis, which lead to increased concentrations of serum triglycer- ides (24), suggesting that the IL6-IL6R cascades are crucial in the metabolism of triglycerides. Observations from previous studies (22,23,25,26) and the present observations, therefore, demonstrated that rs4845625 of IL6R is a susceptibility locus for increased serum triglycerides levels. The rs46522 of UBE2Z was significantly associated with hypertriglyceridemia.…”

Interleukin-6 Receptor Polymorphisms Contribute to the Neurological Status of Korean Patients with Ischemic Stroke

“…In addition, the IL-6R variant interacts with CRP in relation to diabetes risk. In another study, the IL-6R gene (rs4845617) was suggested to play an important role in the pathogenesis of dyslipidemia and atherosclerosis ( 36 ). We identified SNPs of IL-6R, in coding regions near the promoter region, that had greater than 0.1 heterozygosity and greater than 0.1 minor allele frequency.…”

Increased Gustatory Response Score in Obesity and Association Levels with IL-6 and Leptin

“…It has been reported that increased IL-6 levels in metabolic dysregulations can promote adiposity [ 38 ]. In a study conducted on atherosclerosis, IL-6 has been shown to play a pathophysiological role altering lipoprotein lipase (LPL) activity and stimulating lipolysis [ 39 ].…”

“…Leptin is a 16 kDa pleiotropic protein [ 38 , 39 ] mainly secreted by white adipose tissue [ 40 ] by the ob gene [ 41 ]. In addition to its metabolic and endocrine functions, leptin regulates energy expenditure and food intake through a direct effect on hypothalamus [ 41 , 42 ].…”