Dataset Information

Omega-3 Fatty Acids and Genome-Wide Interaction Analyses Reveal DPP10-Pulmonary Function Association.

ABSTRACT:

Rationale

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have anti-inflammatory properties that could benefit adults with comprised pulmonary health.

Objective

To investigate n-3 PUFA associations with spirometric measures of pulmonary function tests (PFTs) and determine underlying genetic susceptibility.

Methods

Associations of n-3 PUFA biomarkers (α-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid [DPA], and docosahexaenoic acid [DHA]) were evaluated with PFTs (FEV₁, FVC, and FEV₁/FVC) in meta-analyses across seven cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (N = 16,134 of European or African ancestry). PFT-associated n-3 PUFAs were carried forward to genome-wide interaction analyses in the four largest cohorts (N = 11,962) and replicated in one cohort (N = 1,687). Cohort-specific results were combined using joint 2 degree-of-freedom (2df) meta-analyses of SNP associations and their interactions with n-3 PUFAs.

Results

DPA and DHA were positively associated with FEV₁ and FVC (P < 0.025), with evidence for effect modification by smoking and by sex. Genome-wide analyses identified a novel association of rs11693320-an intronic DPP10 SNP-with FVC when incorporating an interaction with DHA, and the finding was replicated (P_2df = 9.4 × 10^-9 across discovery and replication cohorts). The rs11693320-A allele (frequency, ∼80%) was associated with lower FVC (P_SNP = 2.1 × 10^-9; β_SNP = -161.0 ml), and the association was attenuated by higher DHA levels (P_{SNP×DHA interaction} = 2.1 × 10^-7; β_{SNP×DHA interaction} = 36.2 ml).

Conclusions

We corroborated beneficial effects of n-3 PUFAs on pulmonary function. By modeling genome-wide n-3 PUFA interactions, we identified a novel DPP10 SNP association with FVC that was not detectable in much larger studies ignoring this interaction.

SUBMITTER: Xu J

PROVIDER: S-EPMC6396866 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Publications

Omega-3 Fatty Acids and Genome-Wide Interaction Analyses Reveal DPP10-Pulmonary Function Association.

Xu Jiayi J Gaddis Nathan C NC Bartz Traci M TM Hou Ruixue R Manichaikul Ani W AW Pankratz Nathan N Smith Albert V AV Sun Fangui F Terzikhan Natalie N Markunas Christina A CA Patchen Bonnie K BK Schu Matthew M Beydoun May A MA Brusselle Guy G GG Eiriksdottir Gudny G Zhou Xia X Wood Alexis C AC Graff Mariaelisa M Harris Tamara B TB Ikram M Arfan MA Jacobs David R DR Launer Lenore J LJ Lemaitre Rozenn N RN O'Connor George T GT Oelsner Elizabeth C EC Psaty Bruce M BM Vasan Ramachandran S RS Rohde Rebecca R RR Rich Stephen S SS Rotter Jerome I JI Seshadri Sudha S Smith Lewis J LJ Tiemeier Henning H Tsai Michael Y MY Uitterlinden André G AG Voruganti V Saroja VS Xu Hanfei H Zilhão Nuno R NR Fornage Myriam M Zillikens M Carola MC London Stephanie J SJ Barr R Graham RG Dupuis Josée J Gharib Sina A SA Gudnason Vilmundur V Lahousse Lies L North Kari E KE Steffen Lyn M LM Cassano Patricia A PA Hancock Dana B DB

American journal of respiratory and critical care medicine 20190301 5

<h4>Rationale</h4>Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have anti-inflammatory properties that could benefit adults with comprised pulmonary health.<h4>Objective</h4>To investigate n-3 PUFA associations with spirometric measures of pulmonary function tests (PFTs) and determine underlying genetic susceptibility.<h4>Methods</h4>Associations of n-3 PUFA biomarkers (α-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid [DPA], and docosahexaenoic acid [DHA]) were evaluated with PFT ...[more]

PMID: 30199657

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Project description:Background and objectivesKidney function gradually decreases with age, and myocardial infarction accelerates this deterioration. Omega-3 (n-3) fatty acids may slow down the decline of kidney function. The effect of marine and plant-derived n-3 fatty acids on kidney function in patients after myocardial infarction was examined.Design, setting, participants, & measurementsIn the Alpha Omega Trial, 2344 patients with history of myocardial infarction ages 60-80 years old (81% men) were randomized to one of four trial margarines. The patients received an additional targeted amount of 400 mg/d eicosapentaenoic acid and docosahexaenoic acid, 2 g/d α-linolenic acid, eicosapentaenoic acid-docosahexaenoic acid plus α-linolenic acid, or placebo for 40 months. Serum cystatin C and serum creatinine were assessed at baseline and after 40 months. Creatinine-cystatin C-based GFR was estimated with the Chronic Kidney Disease Epidemiology Collaboration equation.ResultsPatients consumed 19.9 g margarine/d, providing an additional 239 mg/d eicosapentaenoic acid with 159 mg/d docosahexaenoic acid, 1.99 g/d α-linolenic acid, or both in the active treatment groups. After 40 months, compared with baseline, mean (±SD) creatinine-cystatin C-based GFR was -6.9 (±12.6), -4.8 (±13.4), -6.2 (±12.8), and -6.0 (±13.0) ml/min per 1.73 m(2) in the placebo, eicosapentaenoic acid-docosahexaenoic acid, α-linolenic acid, and eicosapentaenoic acid-docosahexaenoic acid plus α-linolenic acid groups, respectively. After 40 months, in patients receiving eicosapentaenoic acid-docosahexaenoic acid compared with placebo, the decline in creatinine-cystatin C-based GFR was 2.1 less (95% confidence interval, 0.6 to 3.6; P<0.01) ml/min per 1.73 m(2); other comparisons were not statistical significant. Odds ratios (95% confidence intervals) of incident CKD (<60 ml/min per 1.73 m(2)) and rapid decline of kidney function (≥3 ml/min per year) for eicosapentaenoic acid-docosahexaenoic acid compared with placebo were 0.83 (0.58 to 1.18) and 0.85 (0.67 to 1.08), respectively.ConclusionsLong-term supplementation with 400 mg/d eicosapentaenoic acid-docosahexaenoic acid provides a small beneficial effect on kidney function in patients with a history of myocardial infarction.

Project description:BackgroundPreclinical experiments suggest protective effects of omega-3 fatty acids and their metabolites in lung injury and fibrosis. Whether higher intake of omega-3 fatty acids is associated with disease progression and survival in humans with pulmonary fibrosis is unknown.Research questionWhat are the associations of plasma omega-3 fatty acid levels (a validated marker of omega-3 nutritional intake) with disease progression and transplant-free survival in pulmonary fibrosis?Study design and methodsOmega-3 fatty acid levels were measured from plasma samples of patients with clinically diagnosed pulmonary fibrosis from the Pulmonary Fibrosis Foundation Patient Registry (n = 150), University of Virginia (n = 58), and University of Chicago (n = 101) cohorts. The N-3 index (docosahexaenoic acid + eicosapentaenoic acid) was the primary exposure variable of interest. Linear-mixed effects models with random intercept and slope were used to examine associations of plasma omega-3 fatty acid levels with changes in FVC and diffusing capacity for carbon monoxide over a period of 12 months. Cox proportional hazards models were used to examine transplant-free survival. Stratified analyses by telomere length were performed in the University of Chicago cohort.ResultsMost of the cohort were patients with idiopathic pulmonary fibrosis (88%) and male patients (74%). One-unit increment in log-transformed N-3 index plasma level was associated with a change in diffusing capacity for carbon monoxide of 1.43 mL/min/mm Hg per 12 months (95% CI, 0.46-2.41) and a hazard ratio for transplant-free survival of 0.44 (95% CI, 0.24-0.83). Cardiovascular disease history, smoking, and antifibrotic usage did not significantly modify associations. Omega-3 fatty acid levels were not significantly associated with changes in FVC. Higher eicosapentaenoic acid plasma levels were associated with longer transplant-free survival among University of Chicago participants with shorter telomere length (P value for interaction = .02).InterpretationFurther research is needed to investigate underlying biological mechanisms and whether omega-3 fatty acids are a potential disease-modifying therapy.

Dataset Information

Omega-3 Fatty Acids and Genome-Wide Interaction Analyses Reveal DPP10-Pulmonary Function Association.

Rationale

Objective

Methods

Results

Conclusions

Publications

Omega-3 Fatty Acids and Genome-Wide Interaction Analyses Reveal DPP10-Pulmonary Function Association.

Similar Datasets

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