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Genomics of post-prandial lipidomic phenotypes in the Genetics of Lipid lowering Drugs and Diet Network (GOLDN) study.

Irvin MR, Zhi D, Aslibekyan S, Claas SA, Absher DM, Ordovas JM, Tiwari HK, Watkins S, Arnett DK - PLoS ONE (2014)

Bottom Line: After the PPL challenge, fatty acids increased as well as sterols associated with cholesterol absorption, while sterols associated with cholesterol synthesis decreased.Two SNPs (rs12247017 and rs12240292) in the sorbin and SH3 domain containing 1 (SORBS1) gene were associated with b-Sitosterol after correction for multiple testing (P≤4.5*10(-10)).Integration of lipidomic and genomic data has the potential to identify new biomarkers of CVD risk.

View Article: PubMed Central - PubMed

Affiliation: Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.

ABSTRACT

Background: Increased postprandial lipid (PPL) response to dietary fat intake is a heritable risk factor for cardiovascular disease (CVD). Variability in postprandial lipids results from the complex interplay of dietary and genetic factors. We hypothesized that detailed lipid profiles (eg, sterols and fatty acids) may help elucidate specific genetic and dietary pathways contributing to the PPL response.

Methods and results: We used gas chromatography mass spectrometry to quantify the change in plasma concentration of 35 fatty acids and 11 sterols between fasting and 3.5 hours after the consumption of a high-fat meal (PPL challenge) among 40 participants from the GOLDN study. Correlations between sterols, fatty acids and clinical measures were calculated. Mixed linear regression was used to evaluate associations between lipidomic profiles and genomic markers including single nucleotide polymorphisms (SNPs) and methylation markers derived from the Affymetrix 6.0 array and the Illumina Methyl450 array, respectively. After the PPL challenge, fatty acids increased as well as sterols associated with cholesterol absorption, while sterols associated with cholesterol synthesis decreased. PPL saturated fatty acids strongly correlated with triglycerides, very low-density lipoprotein, and chylomicrons. Two SNPs (rs12247017 and rs12240292) in the sorbin and SH3 domain containing 1 (SORBS1) gene were associated with b-Sitosterol after correction for multiple testing (P≤4.5*10(-10)). SORBS1 has been linked to obesity and insulin signaling. No other markers reached the genome-wide significance threshold, yet several other biologically relevant loci are highlighted (eg, PRIC285, a co-activator of PPARa).

Conclusions: Integration of lipidomic and genomic data has the potential to identify new biomarkers of CVD risk.

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Related in: MedlinePlus

Data from 40 Genetics of Lipid Lowering Drugs and Diet Network Study participants.1a (below the diagonal)-Pairwise correlation of fasting sterols (bold), fatty acids (bold), clinical lipids, inflammatory markers, and other clinical measures. 1b (above the diagonal)- Pairwise correlation of change in postprandial sterols (bold), fatty acids (bold), clinical lipids, and other clinical measures. Grey lines indicate clinical parameters not captured postprandially.
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pone-0099509-g001: Data from 40 Genetics of Lipid Lowering Drugs and Diet Network Study participants.1a (below the diagonal)-Pairwise correlation of fasting sterols (bold), fatty acids (bold), clinical lipids, inflammatory markers, and other clinical measures. 1b (above the diagonal)- Pairwise correlation of change in postprandial sterols (bold), fatty acids (bold), clinical lipids, and other clinical measures. Grey lines indicate clinical parameters not captured postprandially.

Mentions: Participants were on average 51.2±13 years old, 55% were male, and 60% were recruited from the GOLDN Minneapolis field center. For a comparison of clinically measured lipids at fasting and 3.5 hours after the intervention and other relevant variables measured in GOLDN among the 40 participants see Table S1. Mean concentration for each of the 11 sterols and 35 fatty acids are presented in Table 1. The average fasting values of each metabolite were within the normal range set by TrueMass internal standards and representative of the assay's typical performance. On average campesterol, b-sitosterol, desmosterol, coprostanol, and cholestanol increased 3.5 hours after the high-fat diet intervention and lathosterol and lanosterol decreased. Stigmasterol, 7-dehydrocholesterol, and 7a-hydroxycholesterol did not significantly change. Overall, total plasma fatty acids increased postprandially (Table 1). Pairwise correlations between fasting clinical measures, inflammatory markers, and newly captured fatty acids and sterols are presented in Figure 1a. In the fasting state, inflammatory markers, BMI, insulin and glucose did not strongly correlate with clinical lipids, fatty acids, or sterols. Fatty acids were strongly and positively correlated with each other in addition to TG and VLDL-C. The strongest correlations observed were among TG, VLDL-C, oleic acid and vaccenic acid. LDL-C and total cholesterol moderately correlated with plasmalogens and longer chain saturated fatty acids. Sterols, including stigmasterol, campesterol, b-sitosterol, and cholestanol, were strongly and positively correlated in the fasting state while lanosterol and lathasterol were negatively correlated with those sterols. Figure 1b shows pairwise correlations among the changes in PPL clinical lipids, fatty acids, and sterols. Many of the observed trends were consistent with that observed at fasting or were stronger, particularly saturated fatty acids (palmitic acid, pentadecanoic acid, myristic acid, and stearic acid) and their biosynthetic products (myristoleic acid, vaccenic acid, oleic acid, and elaidic acid) were strongly correlated with VLDL-C and TG. In the postprandial state, change in chylomicrons positively correlated with that group while change HDL-C negatively correlated with that group.


Genomics of post-prandial lipidomic phenotypes in the Genetics of Lipid lowering Drugs and Diet Network (GOLDN) study.

Irvin MR, Zhi D, Aslibekyan S, Claas SA, Absher DM, Ordovas JM, Tiwari HK, Watkins S, Arnett DK - PLoS ONE (2014)

Data from 40 Genetics of Lipid Lowering Drugs and Diet Network Study participants.1a (below the diagonal)-Pairwise correlation of fasting sterols (bold), fatty acids (bold), clinical lipids, inflammatory markers, and other clinical measures. 1b (above the diagonal)- Pairwise correlation of change in postprandial sterols (bold), fatty acids (bold), clinical lipids, and other clinical measures. Grey lines indicate clinical parameters not captured postprandially.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4048279&req=5

pone-0099509-g001: Data from 40 Genetics of Lipid Lowering Drugs and Diet Network Study participants.1a (below the diagonal)-Pairwise correlation of fasting sterols (bold), fatty acids (bold), clinical lipids, inflammatory markers, and other clinical measures. 1b (above the diagonal)- Pairwise correlation of change in postprandial sterols (bold), fatty acids (bold), clinical lipids, and other clinical measures. Grey lines indicate clinical parameters not captured postprandially.
Mentions: Participants were on average 51.2±13 years old, 55% were male, and 60% were recruited from the GOLDN Minneapolis field center. For a comparison of clinically measured lipids at fasting and 3.5 hours after the intervention and other relevant variables measured in GOLDN among the 40 participants see Table S1. Mean concentration for each of the 11 sterols and 35 fatty acids are presented in Table 1. The average fasting values of each metabolite were within the normal range set by TrueMass internal standards and representative of the assay's typical performance. On average campesterol, b-sitosterol, desmosterol, coprostanol, and cholestanol increased 3.5 hours after the high-fat diet intervention and lathosterol and lanosterol decreased. Stigmasterol, 7-dehydrocholesterol, and 7a-hydroxycholesterol did not significantly change. Overall, total plasma fatty acids increased postprandially (Table 1). Pairwise correlations between fasting clinical measures, inflammatory markers, and newly captured fatty acids and sterols are presented in Figure 1a. In the fasting state, inflammatory markers, BMI, insulin and glucose did not strongly correlate with clinical lipids, fatty acids, or sterols. Fatty acids were strongly and positively correlated with each other in addition to TG and VLDL-C. The strongest correlations observed were among TG, VLDL-C, oleic acid and vaccenic acid. LDL-C and total cholesterol moderately correlated with plasmalogens and longer chain saturated fatty acids. Sterols, including stigmasterol, campesterol, b-sitosterol, and cholestanol, were strongly and positively correlated in the fasting state while lanosterol and lathasterol were negatively correlated with those sterols. Figure 1b shows pairwise correlations among the changes in PPL clinical lipids, fatty acids, and sterols. Many of the observed trends were consistent with that observed at fasting or were stronger, particularly saturated fatty acids (palmitic acid, pentadecanoic acid, myristic acid, and stearic acid) and their biosynthetic products (myristoleic acid, vaccenic acid, oleic acid, and elaidic acid) were strongly correlated with VLDL-C and TG. In the postprandial state, change in chylomicrons positively correlated with that group while change HDL-C negatively correlated with that group.

Bottom Line: After the PPL challenge, fatty acids increased as well as sterols associated with cholesterol absorption, while sterols associated with cholesterol synthesis decreased.Two SNPs (rs12247017 and rs12240292) in the sorbin and SH3 domain containing 1 (SORBS1) gene were associated with b-Sitosterol after correction for multiple testing (P≤4.5*10(-10)).Integration of lipidomic and genomic data has the potential to identify new biomarkers of CVD risk.

View Article: PubMed Central - PubMed

Affiliation: Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.

ABSTRACT

Background: Increased postprandial lipid (PPL) response to dietary fat intake is a heritable risk factor for cardiovascular disease (CVD). Variability in postprandial lipids results from the complex interplay of dietary and genetic factors. We hypothesized that detailed lipid profiles (eg, sterols and fatty acids) may help elucidate specific genetic and dietary pathways contributing to the PPL response.

Methods and results: We used gas chromatography mass spectrometry to quantify the change in plasma concentration of 35 fatty acids and 11 sterols between fasting and 3.5 hours after the consumption of a high-fat meal (PPL challenge) among 40 participants from the GOLDN study. Correlations between sterols, fatty acids and clinical measures were calculated. Mixed linear regression was used to evaluate associations between lipidomic profiles and genomic markers including single nucleotide polymorphisms (SNPs) and methylation markers derived from the Affymetrix 6.0 array and the Illumina Methyl450 array, respectively. After the PPL challenge, fatty acids increased as well as sterols associated with cholesterol absorption, while sterols associated with cholesterol synthesis decreased. PPL saturated fatty acids strongly correlated with triglycerides, very low-density lipoprotein, and chylomicrons. Two SNPs (rs12247017 and rs12240292) in the sorbin and SH3 domain containing 1 (SORBS1) gene were associated with b-Sitosterol after correction for multiple testing (P≤4.5*10(-10)). SORBS1 has been linked to obesity and insulin signaling. No other markers reached the genome-wide significance threshold, yet several other biologically relevant loci are highlighted (eg, PRIC285, a co-activator of PPARa).

Conclusions: Integration of lipidomic and genomic data has the potential to identify new biomarkers of CVD risk.

Show MeSH
Related in: MedlinePlus