Single nucleotide polymorphisms in CETP, SLC46A1, SLC19A1, CD36, BCMO1, APOA5, and ABCA1 are significant predictors of plasma HDL in healthy adults

Lipids Health Dis. 2013 May 8:12:66. doi: 10.1186/1476-511X-12-66.

Abstract

Background: In a marker-trait association study we estimated the statistical significance of 65 single nucleotide polymorphisms (SNP) in 23 candidate genes on HDL levels of two independent Caucasian populations. Each population consisted of men and women and their HDL levels were adjusted for gender and body weight. We used a linear regression model. Selected genes corresponded to folate metabolism, vitamins B-12, A, and E, and cholesterol pathways or lipid metabolism.

Methods: Extracted DNA from both the Sacramento and Beltsville populations was analyzed using an allele discrimination assay with a MALDI-TOF mass spectrometry platform. The adjusted phenotype, y, was HDL levels adjusted for gender and body weight only statistical analyses were performed using the genotype association and regression modules from the SNP Variation Suite v7.

Results: Statistically significant SNP (where P values were adjusted for false discovery rate) included: CETP (rs7499892 and rs5882); SLC46A1 (rs37514694; rs739439); SLC19A1 (rs3788199); CD36 (rs3211956); BCMO1 (rs6564851), APOA5 (rs662799), and ABCA1 (rs4149267). Many prior association trends of the SNP with HDL were replicated in our cross-validation study. Significantly, the association of SNP in folate transporters (SLC46A1 rs37514694 and rs739439; SLC19A1 rs3788199) with HDL was identified in our study.

Conclusions: Given recent literature on the role of niacin in the biogenesis of HDL, focus on status and metabolism of B-vitamins and metabolites of eccentric cleavage of β-carotene with lipid metabolism is exciting for future study.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP Binding Cassette Transporter 1 / genetics
  • Adult
  • Aged
  • Apolipoprotein A-V
  • Apolipoproteins A / genetics
  • CD36 Antigens / genetics
  • Cholesterol / blood*
  • Cholesterol Ester Transfer Proteins / genetics
  • Female
  • Folic Acid Transporters / genetics*
  • Genetic Association Studies*
  • Humans
  • Lipoproteins, HDL / blood*
  • Lipoproteins, HDL / genetics
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Proton-Coupled Folate Transporter / genetics
  • Reduced Folate Carrier Protein / genetics
  • beta-Carotene 15,15'-Monooxygenase / genetics

Substances

  • ABCA1 protein, human
  • APOA5 protein, human
  • ATP Binding Cassette Transporter 1
  • Apolipoprotein A-V
  • Apolipoproteins A
  • CD36 Antigens
  • CETP protein, human
  • Cholesterol Ester Transfer Proteins
  • Folic Acid Transporters
  • Lipoproteins, HDL
  • Proton-Coupled Folate Transporter
  • Reduced Folate Carrier Protein
  • SLC19A1 protein, human
  • SLC46A1 protein, human
  • Cholesterol
  • BCO1 protein, human
  • beta-Carotene 15,15'-Monooxygenase