@article {6687, title = {Dietary fatty acids modulate associations between genetic variants and circulating fatty acids in plasma and erythrocyte membranes: Meta-analysis of nine studies in the CHARGE consortium.}, journal = {Mol Nutr Food Res}, volume = {59}, year = {2015}, month = {2015 Jul}, pages = {1373-83}, abstract = {

SCOPE: Tissue concentrations of omega-3 fatty acids may reduce cardiovascular disease risk, and genetic variants are associated with circulating fatty acids concentrations. Whether dietary fatty acids interact with genetic variants to modify circulating omega-3 fatty acids is unclear. We evaluated interactions between genetic variants and fatty acid intakes for circulating alpha-linoleic acid, eicosapentaenoic acid, docosahexaenoic acid, and docosapentaenoic acid.

METHODS AND RESULTS: We conducted meta-analyses (N = 11~668) evaluating interactions between dietary fatty acids and genetic variants (rs174538 and rs174548 in FADS1 (fatty acid desaturase 1), rs7435 in AGPAT3 (1-acyl-sn-glycerol-3-phosphate), rs4985167 in PDXDC1 (pyridoxal-dependent decarboxylase domain-containing 1), rs780094 in GCKR (glucokinase regulatory protein), and rs3734398 in ELOVL2 (fatty acid elongase 2)). Stratification by measurement compartment (plasma versus erthyrocyte) revealed compartment-specific interactions between FADS1 rs174538 and rs174548 and dietary alpha-linolenic acid and linoleic acid for docosahexaenoic acid and docosapentaenoic acid.

CONCLUSION: Our findings reinforce earlier reports that genetically based differences in circulating fatty acids may be partially due to differences in the conversion of fatty acid precursors. Further, fatty acids measurement compartment may modify gene-diet relationships, and considering compartment may improve the detection of gene-fatty acids interactions for circulating fatty acid outcomes.

}, keywords = {Acetyltransferases, Acyltransferases, Adaptor Proteins, Signal Transducing, Carboxy-Lyases, Diet, Docosahexaenoic Acids, Eicosapentaenoic Acid, Erythrocyte Membrane, Fatty Acid Desaturases, Fatty Acids, Fatty Acids, Omega-3, Female, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide}, issn = {1613-4133}, doi = {10.1002/mnfr.201400734}, author = {Smith, Caren E and Follis, Jack L and Nettleton, Jennifer A and Foy, Millennia and Wu, Jason H Y and Ma, Yiyi and Tanaka, Toshiko and Manichakul, Ani W and Wu, Hongyu and Chu, Audrey Y and Steffen, Lyn M and Fornage, Myriam and Mozaffarian, Dariush and Kabagambe, Edmond K and Ferruci, Luigi and Chen, Yii-Der Ida and Rich, Stephen S and Djouss{\'e}, Luc and Ridker, Paul M and Tang, Weihong and McKnight, Barbara and Tsai, Michael Y and Bandinelli, Stefania and Rotter, Jerome I and Hu, Frank B and Chasman, Daniel I and Psaty, Bruce M and Arnett, Donna K and King, Irena B and Sun, Qi and Wang, Lu and Lumley, Thomas and Chiuve, Stephanie E and Siscovick, David S and Ordovas, Jose M and Lemaitre, Rozenn N} } @article {6615, title = {Genetic loci associated with circulating levels of very long-chain saturated fatty acids.}, journal = {J Lipid Res}, volume = {56}, year = {2015}, month = {2015 Jan}, pages = {176-84}, abstract = {

Very long-chain saturated fatty acids (VLSFAs) are saturated fatty acids with 20 or more carbons. In contrast to the more abundant saturated fatty acids, such as palmitic acid, there is growing evidence that circulating VLSFAs may have beneficial biological properties. Whether genetic factors influence circulating levels of VLSFAs is not known. We investigated the association of common genetic variation with plasma phospholipid/erythrocyte levels of three VLSFAs by performing genome-wide association studies in seven population-based cohorts comprising 10,129 subjects of European ancestry. We observed associations of circulating VLSFA concentrations with common variants in two genes, serine palmitoyl-transferase long-chain base subunit 3 (SPTLC3), a gene involved in the rate-limiting step of de novo sphingolipid synthesis, and ceramide synthase 4 (CERS4). The SPTLC3 variant at rs680379 was associated with higher arachidic acid (20:0 , P = 5.81 {\texttimes} 10(-13)). The CERS4 variant at rs2100944 was associated with higher levels of 20:0 (P = 2.65 {\texttimes} 10(-40)) and in analyses that adjusted for 20:0, with lower levels of behenic acid (P = 4.22 {\texttimes} 10(-26)) and lignoceric acid (P = 3.20 {\texttimes} 10(-21)). These novel associations suggest an inter-relationship of circulating VLSFAs and sphingolipid synthesis.

}, keywords = {Cohort Studies, Fatty Acids, Genetic Loci, Genetic Variation, Genome-Wide Association Study, Humans}, issn = {1539-7262}, doi = {10.1194/jlr.M052456}, author = {Lemaitre, Rozenn N and King, Irena B and Kabagambe, Edmond K and Wu, Jason H Y and McKnight, Barbara and Manichaikul, Ani and Guan, Weihua and Sun, Qi and Chasman, Daniel I and Foy, Millennia and Wang, Lu and Zhu, Jingwen and Siscovick, David S and Tsai, Michael Y and Arnett, Donna K and Psaty, Bruce M and Djouss{\'e}, Luc and Chen, Yii-der I and Tang, Weihong and Weng, Lu-Chen and Wu, Hongyu and Jensen, Majken K and Chu, Audrey Y and Jacobs, David R and Rich, Stephen S and Mozaffarian, Dariush and Steffen, Lyn and Rimm, Eric B and Hu, Frank B and Ridker, Paul M and Fornage, Myriam and Friedlander, Yechiel} } @article {6685, title = {Genetic loci associated with circulating phospholipid trans fatty acids: a meta-analysis of genome-wide association studies from the CHARGE Consortium.}, journal = {Am J Clin Nutr}, volume = {101}, year = {2015}, month = {2015 Feb}, pages = {398-406}, abstract = {

BACKGROUND: Circulating trans fatty acids (TFAs), which cannot be synthesized by humans, are linked to adverse health outcomes. Although TFAs are obtained from diet, little is known about subsequent influences (e.g., relating to incorporation, metabolism, or intercompetition with other fatty acids) that could alter circulating concentrations and possibly modulate or mediate impacts on health.

OBJECTIVE: The objective was to elucidate novel biologic pathways that may influence circulating TFAs by evaluating associations between common genetic variation and TFA biomarkers.

DESIGN: We performed meta-analyses using 7 cohorts of European-ancestry participants (n = 8013) having measured genome-wide variation in single-nucleotide polymorphisms (SNPs) and circulating TFA biomarkers (erythrocyte or plasma phospholipids), including trans-16:1n-7, total trans-18:1, trans/cis-18:2, cis/trans-18:2, and trans/trans-18:2. We further evaluated SNPs with genome-wide significant associations among African Americans (n = 1082), Chinese Americans (n = 669), and Hispanic Americans (n = 657) from 2 of these cohorts.

RESULTS: Among European-ancestry participants, 31 SNPs in or near the fatty acid desaturase (FADS) 1 and 2 cluster were associated with cis/trans-18:2; a top hit was rs174548 (β = 0.0035, P = 4.90 {\texttimes} 10(-15)), an SNP previously associated with circulating n-3 and n-6 polyunsaturated fatty acid concentrations. No significant association was identified for other TFAs. rs174548 in FADS1/2 was also associated with cis/trans-18:2 in Hispanic Americans (β = 0.0053, P = 1.05 {\texttimes} 10(-6)) and Chinese Americans (β = 0.0028, P = 0.002) but not African Americans (β = 0.0009, P = 0.34); however, in African Americans, fine mapping identified a top hit in FADS2 associated with cis/trans-18:2 (rs174579: β = 0.0118, P = 4.05 {\texttimes} 10(-5)). The association between rs174548 and cis/trans-18:2 remained significant after further adjustment for individual circulating n-3 and n-6 fatty acids, except arachidonic acid. After adjustment for arachidonic acid concentrations, the association between rs174548 and cis/trans-18:2 was nearly eliminated in European-ancestry participants (β-coefficient reduced by 86\%), with similar reductions in Hispanic Americans and Chinese Americans.

CONCLUSIONS: Our findings provide novel evidence for genetic regulation of cis/trans-18:2 by the FADS1/2 cluster and suggest that this regulation may be influenced/mediated by concentrations of arachidonic acid, an n-6 polyunsaturated fat.

}, keywords = {African Americans, Arachidonic Acid, Asian Americans, Biomarkers, European Continental Ancestry Group, Fatty Acids, Omega-6, Gene Frequency, Genetic Association Studies, Genetic Loci, Genotyping Techniques, Humans, Phospholipids, Polymorphism, Single Nucleotide, Trans Fatty Acids}, issn = {1938-3207}, doi = {10.3945/ajcn.114.094557}, author = {Mozaffarian, Dariush and Kabagambe, Edmond K and Johnson, Catherine O and Lemaitre, Rozenn N and Manichaikul, Ani and Sun, Qi and Foy, Millennia and Wang, Lu and Wiener, Howard and Irvin, Marguerite R and Rich, Stephen S and Wu, Hongyu and Jensen, Majken K and Chasman, Daniel I and Chu, Audrey Y and Fornage, Myriam and Steffen, Lyn and King, Irena B and McKnight, Barbara and Psaty, Bruce M and Djouss{\'e}, Luc and Chen, Ida Y-D and Wu, Jason H Y and Siscovick, David S and Ridker, Paul M and Tsai, Michael Y and Rimm, Eric B and Hu, Frank B and Arnett, Donna K} }