Associations between common genetic polymorphisms in the liver X receptor alpha and its target genes with the serum HDL-cholesterol concentration in adolescents of the HELENA Study

Atherosclerosis. 2011 May;216(1):166-9. doi: 10.1016/j.atherosclerosis.2011.01.031. Epub 2011 Jan 26.

Abstract

Objective: Genetic variability in the NR1H3 gene (encoding LXRα) and in several of its target genes is associated with serum HDL-cholesterol (HDL-C) concentrations. We sought to assess if these associations could be detected in adolescents.

Methods: Thirty-nine polymorphisms in NR1H3, ABCA1, APOE, CETP, PLTP and LPL were analysed in the HELENA study (n = 1144 European adolescents).

Results: The minor alleles of rs11039155 in NR1H3, rs2575879 in ABCA1, rs708272, rs17231506 and rs5882 in CETP and rs328 in LPL were associated with higher serum HDL-C concentrations (p ≤ 0.0012). The minor alleles of rs12221497 in NR1H3, rs1800978 in ABCA1 and the APOE ɛ4 allele were associated with lower HDL-C concentrations (p ≤ 0.01). The combined set of associated polymorphisms accounted for ∼6.6% of the variance in HDL-C.

Conclusion: We report for the first time that polymorphisms in NR1H3 and its target genes ABCA1, APOE, CETP and LPL contribute to the genetic variance for HDL-C concentrations in adolescence.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters / genetics
  • Adolescent
  • Apolipoproteins E / genetics
  • Biomarkers / blood
  • Chi-Square Distribution
  • Cholesterol Ester Transfer Proteins / genetics
  • Cholesterol, HDL / blood*
  • Cross-Sectional Studies
  • Europe
  • Female
  • Gene Frequency
  • Haplotypes
  • Humans
  • Linkage Disequilibrium
  • Lipoprotein Lipase / genetics
  • Liver X Receptors
  • Male
  • Orphan Nuclear Receptors / genetics*
  • Phenotype
  • Phospholipid Transfer Proteins / genetics
  • Polymorphism, Single Nucleotide*

Substances

  • ABCA1 protein, human
  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters
  • Apolipoproteins E
  • Biomarkers
  • CETP protein, human
  • Cholesterol Ester Transfer Proteins
  • Cholesterol, HDL
  • Liver X Receptors
  • NR1H3 protein, human
  • Orphan Nuclear Receptors
  • PLTP protein, human
  • Phospholipid Transfer Proteins
  • LPL protein, human
  • Lipoprotein Lipase