title: Association between interleukin-6 receptor gene variations and atherosclerotic lipid profiles among young adolescents in Taiwan.
abstract: BACKGROUND
  To analyze the potential genetic associations between four polymorphisms of interleukin-6 receptor (IL-6R) gene and atherosclerotic lipid profiles among young adolescents in Taiwan.
  
  
  METHODS
  Using 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.
  
  
  RESULTS
  IL-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).
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Department of Community Medicine, Shuang-Ho Hospital, Taipei Medical University, New Taipei City 235, Taiwan. chuepi@ndmctsgh.edu.tw
authors.forename: Nain-Feng
authors.initials: NF
authors.lastname: Chu
authors.forename: Fu-Hung
authors.initials: FH
authors.lastname: Lin
authors.forename: Hsien-Chuan
authors.initials: HC
authors.lastname: Chin
authors.forename: Ye-Jen
authors.initials: YJ
authors.lastname: Hong
mesh_terms: D000293:Adolescent; D050197:Atherosclerosis / Q000453:epidemiology*; D002648:Child; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D003430:Cross-Sectional Studies; D050171:Dyslipidemias / Q000097:blood* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008055:Lipids / Q000097:blood*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D019947:Receptors, Interleukin-6 / Q000235:genetics*; D012307:Risk Factors; D012720:Severity of Illness Index; D012737:Sex Factors; D013624:Taiwan / Q000453:epidemiology; D014280:Triglycerides / Q000097:blood
chemical_list: D008076:Cholesterol, HDL; C508603:IL6R protein, human; D008055:Lipids; D019947:Receptors, Interleukin-6; D014280:Triglycerides; D002784:Cholesterol