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Genome-wide association study of plasma polyunsaturated fatty acids in the InCHIANTI Study.

ABSTRACT: Polyunsaturated fatty acids (PUFA) have a role in many physiological processes, including energy production, modulation of inflammation, and maintenance of cell membrane integrity. High plasma PUFA concentrations have been shown to have beneficial effects on cardiovascular disease and mortality. To identify genetic contributors of plasma PUFA concentrations, we conducted a genome-wide association study of plasma levels of six omega-3 and omega-6 fatty acids in 1,075 participants in the InCHIANTI study on aging. The strongest evidence for association was observed in a region of chromosome 11 that encodes three fatty acid desaturases (FADS1, FADS2, FADS3). The SNP with the most significant association was rs174537 near FADS1 in the analysis of arachidonic acid (AA; p = 5.95 x 10(-46)). Minor allele homozygotes had lower AA compared to the major allele homozygotes and rs174537 accounted for 18.6% of the additive variance in AA concentrations. This SNP was also associated with levels of eicosadienoic acid (EDA; p = 6.78 x 10(-9)) and eicosapentanoic acid (EPA; p = 1.07 x 10(-14)). Participants carrying the allele associated with higher AA, EDA, and EPA also had higher low-density lipoprotein (LDL-C) and total cholesterol levels. Outside the FADS gene cluster, the strongest region of association mapped to chromosome 6 in the region encoding an elongase of very long fatty acids 2 (ELOVL2). In this region, association was observed with EPA (rs953413; p = 1.1 x 10(-6)). The effects of rs174537 were confirmed in an independent sample of 1,076 subjects participating in the GOLDN study. The ELOVL2 SNP was associated with docosapentanoic and DHA but not with EPA in GOLDN. These findings show that polymorphisms of genes encoding enzymes in the metabolism of PUFA contribute to plasma concentrations of fatty acids.

SUBMITTER: Tanaka T

PROVIDER: S-EPMC2613033 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

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Genome-wide association study of plasma polyunsaturated fatty acids in the InCHIANTI Study.

Tanaka Toshiko T Shen Jian J Abecasis Gonçalo R GR Kisialiou Aliaksei A Ordovas Jose M JM Guralnik Jack M JM Singleton Andrew A Bandinelli Stefania S Cherubini Antonio A Arnett Donna D Tsai Michael Y MY Ferrucci Luigi L

PLoS genetics 20090116 1

Polyunsaturated fatty acids (PUFA) have a role in many physiological processes, including energy production, modulation of inflammation, and maintenance of cell membrane integrity. High plasma PUFA concentrations have been shown to have beneficial effects on cardiovascular disease and mortality. To identify genetic contributors of plasma PUFA concentrations, we conducted a genome-wide association study of plasma levels of six omega-3 and omega-6 fatty acids in 1,075 participants in the InCHIANTI ...[more]

PMID: 19148276

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Project description:BACKGROUND/OBJECTIVE:Previous research has focused on associations between dietary fat and body mass index (BMI), but the contributions of different types of fat to BMI remain unclear. The purpose of this study is to estimate whether plasma phospholipid omega-3 (n-3), omega-6 (n-6) or trans fatty acids are associated with BMI at baseline and with subsequent BMI changes over time; and whether total phospholipid n-6 or trans fatty acids modify any association between phospholipid n-3 and BMI. METHODS:Cross-sectional and longitudinal linear mixed models include 6243 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. Participants were 45-84 years old, had no history of cardiovascular disease at baseline (2000-2002) and were followed for up to 10 years. Plasma phospholipid fatty acids were measured using fasting plasma samples at baseline. Fully adjusted models include demographics, health behaviors and other fatty acids (n-3, n-6 and trans) as appropriate. RESULTS:In fully adjusted models, phospholipid n-3 fatty acid levels were inversely associated with baseline BMI (Ptrend <0.001). Baseline BMI was 1.14 (95% confidence interval (CI): 0.71, 1.57) kg?m-2 lower among participants with total n-3 values in the highest vs the lowest quartiles, but was not associated with changes in BMI. Total phospholipid n-6 was positively associated with baseline BMI in partially adjusted but not fully adjusted models. No overall association was observed between fatty acid levels and changes in BMI. No clear association was observed between trans fatty acids and baseline BMI or BMI change. No effect modification in the association between phospholipid n-3 and baseline BMI or BMI change was observed by either phospholipid n-6 or trans fatty acids. CONCLUSIONS:Phospholipid total and specific n-3 fatty acid levels were inversely associated with BMI at baseline, whereas associations tended to be positive for total n-6 fatty acids. Significant associations between fatty acid levels and BMI changes were not observed.

Project description:Calves may experience increased oxidative stress at birth through activation of metabolic and respiratory processes. Reducing oxidative stress may enhance calf viability in early life. Our objective was to determine the dose response to fish and flaxseed oil when supplemented in colostrum on concentrations of plasma fatty acid (FA), FA metabolites, and index of oxidative stress during the critical first week of life in calves to understand how supplementing n-3 FA may decrease oxidative stress. We hypothesized that n-3 FA supplemented in colostrum in a linear dose-dependent fashion would associate with increased plasma n-3 FA concentrations and decreased oxidative stress. Twenty-four male and female Holstein calves were randomly assigned to receive 0, 30, 60, or 120 mL of a 1:1 fish to flaxseed oil supplement in colostrum. All calves received 2.8 L of previously frozen colostrum (≥22% Brix) with their respective treatment within 6 h after birth. Blood was sampled before first feeding after birth and on d 1, 2, 4, 7, and 14 d of age to assess oxidant status and plasma free PUFA, phospholipid FA, and oxylipid concentrations. Health indicators were observed daily. Indicators of general health and growth were unaffected by treatment. Supplemented calves exhibited greater concentrations of n-3 FA in plasma as free and phospholipid FA and some n-3 and n-6 FA-derived oxylipids in the first week of life in a linear fashion with increasing supplemental dose. Fish and flaxseed oil treatments did not alter oxidant status but overall decreased isoprostane concentrations in plasma, indicating oxidative stress was decreased. Together, these responses indicate that the fish and flaxseed oil supplement was antiinflammatory. In conclusion, supplementing colostrum with 30, 60, and 120 mL of a 1:1 mixture of fish and flaxseed oil linearly increased plasma concentrations of n-3 FA and metabolites and decreased biomarkers of oxidative stress, but did not alter oxidant status or affect health or growth. Our findings suggest neonatal calves may benefit from n-3 FA supplementation in colostrum to encourage a greater antiinflammatory state.

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Genome-wide association study of plasma polyunsaturated fatty acids in the InCHIANTI Study.

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Genome-wide association study of plasma polyunsaturated fatty acids in the InCHIANTI Study.

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