|ANDREW, CLIFFORD - University Of California|
|GONZALO, RINCON - University Of California|
|JANEL, OWENS - University Of California|
|JUAN, MEDRANO - University Of California|
Submitted to: Lipids in Health and Disease
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/2/2013
Publication Date: 5/8/2013
Citation: Andrew, C.J., Gonzalo, R., Janel, O., Juan, M., Moshfegh, A.J., Baer, D.J., Novotny Dura, J. 2013. Single nucleotide polymorphisms in CETP, SLC46A1, SLC19A1, CD36, BCOM1, APOA5, and ABCA1 are significant predictors of plasma HDL in healthy adults. Lipids in Health and Disease. 12:66-75.
Interpretive Summary: The amount of cholesterol carried in blood in high density lipoprotein (HDL) particles is an indicator of heart disease risk, with high levels being favorable. Dietary factors can influence HDL cholesterol levels, but individual responses to dietary interventions can be quite variable. A major factor in determining individual response to nutrient intervention is genotype. Therefore, we investigated deviations in genes that code for proteins involved in physiologic pathways related to HDL cholesterol. Blood samples were drawn from 759 individuals, and HDL cholesterol levels were measured, and deviations in 23 genes were determined. We used a mathematical technique called linear regression to determine which gene deviations were associated with higher or lower HDL cholesterol levels. Deviations in many genes were associated with HDL cholesterol levels, including cholesterol ester transfer protein (which moves cholesterol among lipoproteins), beta-carotene mono-oxygenase 1 (which converts beta-carotene to vitamin A), and transporters that move the vitamin folate into cells. Given recent literature on the role of niacin in the manufacturing of HDL particles, further investigation on B-vitamin status and metabolism of beta-carotene and their influence on risk for cardiovascular disease will yield exciting new results. This information will be useful for scientists studying folate and B vitamin metabolism, and health professionals studying heart disease.
Technical Abstract: 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. 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. 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 beta-carotene with lipid metabolism is exciting for future study.