TY - JOUR T1 - Circulating and dietary α-linolenic acid and incidence of congestive heart failure in older adults: the Cardiovascular Health Study. JF - Am J Clin Nutr Y1 - 2012 A1 - Lemaitre, Rozenn N A1 - Sitlani, Colleen A1 - Song, Xiaoling A1 - King, Irena B A1 - McKnight, Barbara A1 - Spiegelman, Donna A1 - Sacks, Frank M A1 - Djoussé, Luc A1 - Rimm, Eric B A1 - Siscovick, David S A1 - Mozaffarian, Dariush KW - Aged KW - Alcohol Drinking KW - alpha-Linolenic Acid KW - Biomarkers KW - Body Mass Index KW - Cardiovascular Diseases KW - Diet KW - Fatty Acid Desaturases KW - Female KW - Follow-Up Studies KW - Heart Failure KW - Humans KW - Incidence KW - Male KW - Polymorphism, Single Nucleotide KW - Prevalence KW - Prospective Studies KW - Risk Factors KW - Smoking KW - Surveys and Questionnaires KW - United States AB -

BACKGROUND: Few studies have evaluated the association between the n-3 fatty acid α-linolenic acid (ALA) and the incidence of congestive heart failure (CHF).

OBJECTIVE: We investigated whether plasma phospholipid concentrations and estimated dietary consumption of ALA are associated with incident CHF.

DESIGN: We used data from the Cardiovascular Health Study, a prospective cohort study of cardiovascular diseases among adults aged ≥65 y, from 4 US communities. A total of 2957 participants free of prevalent heart disease and with available fatty acid measurements were included in biomarker analyses (30,722 person-years and 686 incident CHF events). A total of 4432 participants free of prevalent heart disease were included in dietary analyses (52,609 person-years and 1072 events). We investigated the association of ALA with incident CHF by using Cox regression.

RESULTS: After adjustment for age, sex, race, education, smoking status, BMI, waist circumference, and alcohol consumption, plasma phospholipid ALA was not associated with incident CHF (HR for the highest compared with the lowest quartile: 0.97; 95% CI: 0.79, 1.21; P-trend = 0.85). Likewise, dietary ALA was not associated with incident CHF (adjusted HR for the highest compared with the lowest quartile: 0.96; 95% CI: 0.82, 1.20; P-trend = 0.97). We observed no association of biomarker or dietary ALA with nonvalvular CHF subtype. We also found little evidence of an association between ALA and CHF in subgroups based on age, sex, diabetes, fish consumption, BMI, or FADS2 genotype (rs1535).

CONCLUSION: ALA intake is not associated with incident CHF in older adults. This trial was registered at clinicaltrials.gov as NCT00005133.

VL - 96 IS - 2 U1 - http://www.ncbi.nlm.nih.gov/pubmed/22743310?dopt=Abstract ER - TY - JOUR T1 - Genome-wide association study of plasma N6 polyunsaturated fatty acids within the cohorts for heart and aging research in genomic epidemiology consortium. JF - Circ Cardiovasc Genet Y1 - 2014 A1 - Guan, Weihua A1 - Steffen, Brian T A1 - Lemaitre, Rozenn N A1 - Wu, Jason H Y A1 - Tanaka, Toshiko A1 - Manichaikul, Ani A1 - Foy, Millennia A1 - Rich, Stephen S A1 - Wang, Lu A1 - Nettleton, Jennifer A A1 - Tang, Weihong A1 - Gu, Xiangjun A1 - Bandinelli, Stafania A1 - King, Irena B A1 - McKnight, Barbara A1 - Psaty, Bruce M A1 - Siscovick, David A1 - Djoussé, Luc A1 - Chen, Yii-Der Ida A1 - Ferrucci, Luigi A1 - Fornage, Myriam A1 - Mozafarrian, Dariush A1 - Tsai, Michael Y A1 - Steffen, Lyn M KW - Adult KW - Aged KW - Aged, 80 and over KW - Aging KW - Chromosomes, Human, Pair 10 KW - Chromosomes, Human, Pair 16 KW - Chromosomes, Human, Pair 6 KW - Fatty Acid Desaturases KW - Fatty Acids, Omega-6 KW - Female KW - Genome-Wide Association Study KW - Genomics KW - Heart Diseases KW - Humans KW - Male KW - Middle Aged KW - Polymorphism, Single Nucleotide KW - Prospective Studies KW - Sequence Analysis, DNA AB -

BACKGROUND: Omega6 (n6) polyunsaturated fatty acids (PUFAs) and their metabolites are involved in cell signaling, inflammation, clot formation, and other crucial biological processes. Genetic components, such as variants of fatty acid desaturase (FADS) genes, determine the composition of n6 PUFAs.

METHODS AND RESULTS: To elucidate undiscovered biological pathways that may influence n6 PUFA composition, we conducted genome-wide association studies and meta-analyses of associations of common genetic variants with 6 plasma n6 PUFAs in 8631 white adults (55% women) across 5 prospective studies. Plasma phospholipid or total plasma fatty acids were analyzed by similar gas chromatography techniques. The n6 fatty acids linoleic acid (LA), γ-linolenic acid (GLA), dihomo-GLA, arachidonic acid, and adrenic acid were expressed as percentage of total fatty acids. We performed linear regression with robust SEs to test for single-nucleotide polymorphism-fatty acid associations, with pooling using inverse-variance-weighted meta-analysis. Novel regions were identified on chromosome 10 associated with LA (rs10740118; P=8.1×10(-9); near NRBF2), on chromosome 16 with LA, GLA, dihomo-GLA, and arachidonic acid (rs16966952; P=1.2×10(-15), 5.0×10(-11), 7.6×10(-65), and 2.4×10(-10), respectively; NTAN1), and on chromosome 6 with adrenic acid after adjustment for arachidonic acid (rs3134950; P=2.1×10(-10); AGPAT1). We confirmed previous findings of the FADS cluster on chromosome 11 with LA and arachidonic acid, and further observed novel genome-wide significant association of this cluster with GLA, dihomo-GLA, and adrenic acid (P=2.3×10(-72), 2.6×10(-151), and 6.3×10(-140), respectively).

CONCLUSIONS: Our findings suggest that along with the FADS gene cluster, additional genes may influence n6 PUFA composition.

VL - 7 IS - 3 U1 - http://www.ncbi.nlm.nih.gov/pubmed/24823311?dopt=Abstract ER - TY - JOUR T1 - 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. JF - Mol Nutr Food Res Y1 - 2015 A1 - Smith, Caren E A1 - Follis, Jack L A1 - Nettleton, Jennifer A A1 - Foy, Millennia A1 - Wu, Jason H Y A1 - Ma, Yiyi A1 - Tanaka, Toshiko A1 - Manichakul, Ani W A1 - Wu, Hongyu A1 - Chu, Audrey Y A1 - Steffen, Lyn M A1 - Fornage, Myriam A1 - Mozaffarian, Dariush A1 - Kabagambe, Edmond K A1 - Ferruci, Luigi A1 - Chen, Yii-Der Ida A1 - Rich, Stephen S A1 - Djoussé, Luc A1 - Ridker, Paul M A1 - Tang, Weihong A1 - McKnight, Barbara A1 - Tsai, Michael Y A1 - Bandinelli, Stefania A1 - Rotter, Jerome I A1 - Hu, Frank B A1 - Chasman, Daniel I A1 - Psaty, Bruce M A1 - Arnett, Donna K A1 - King, Irena B A1 - Sun, Qi A1 - Wang, Lu A1 - Lumley, Thomas A1 - Chiuve, Stephanie E A1 - Siscovick, David S A1 - Ordovas, Jose M A1 - Lemaitre, Rozenn N KW - Acetyltransferases KW - Acyltransferases KW - Adaptor Proteins, Signal Transducing KW - Carboxy-Lyases KW - Diet KW - Docosahexaenoic Acids KW - Eicosapentaenoic Acid KW - Erythrocyte Membrane KW - Fatty Acid Desaturases KW - Fatty Acids KW - Fatty Acids, Omega-3 KW - Female KW - Humans KW - Male KW - Middle Aged KW - Polymorphism, Single Nucleotide AB -

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.

VL - 59 IS - 7 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25626431?dopt=Abstract ER -