Abstract

BackgroundIn 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.MethodsExtracted 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.ResultsStatistically 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.ConclusionsGiven 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.

Highlights

  • In a marker-trait association study we estimated the statistical significance of 65 single nucleotide polymorphisms (SNP) in 23 candidate genes on high-density lipoprotein (HDL) levels of two independent Caucasian populations

  • In our recent work [2], we investigated 65 single nucleotide polymorphisms (SNP) in 23 candidate genes involved in folate metabolism (8 genes), vitamins B-12, A, and E metabolism (5 genes), and cholesterol pathways or lipid metabolism (10 genes) in a homocysteine/red blood cell folate marker trait association study

  • A few SNP associated with diabetes mellitus (DM), cardiovascular disease (CVD) and maintenance of the cholesterol pathway or lipid metabolism were identified: serine palmitoyltransferase (SPTLC1 rs117 90991), cholesteryl ester transfer protein (CETP rs5882) and scavenger receptor class B type 1 (SCARB1 rs838892)

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Summary

Introduction

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. In our recent work [2], we investigated 65 single nucleotide polymorphisms (SNP) in 23 candidate genes involved in folate metabolism (8 genes), vitamins B-12, A, and E metabolism (5 genes), and cholesterol pathways or lipid metabolism (10 genes) in a homocysteine/red blood cell folate marker trait association study. SNP associated with transfer of antioxidant vitamins, including rs2118981 in the cellular retinol binding protein II gene (CRBP2), which is important for vitamin A and retinoid transfer, and rs838892 SCARB1 (for tocopherols and tocotrienols), were statistically significant predictors in the final model. SNP in betaine-homocysteine methyltransferase (BHMT rs3733890) and methylene tetrahydrofolate reductase (MTHFR rs1801131), both of which are involved in one-carbon metabolism, were included in the final model that was previously described [2]

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