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Network Analysis Identifies NR4A2 with Gene‐Environment Interactions Influencing Inflammation Biomarkers Modified by Fatty Acid Intake in Two Populations
Author(s) -
Hou Ruixue,
Parnell Laurence,
Lai ChaoQiang,
Kamanu Frederick,
Ordovas Jose,
Smith Caren
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.750.4
Subject(s) - inflammation , mediterranean diet , polyunsaturated fatty acid , biology , genotype , snp , gene , single nucleotide polymorphism , fatty acid , genetics , immunology , medicine , biochemistry
Background Chronic inflammation is an important component of cardiometabolic diseases. Markers of inflammation are sensitive to both genetic variation and diet, particularly different dietary fatty acids. Objective We built a nutrition‐inflammation‐CVD biological network to identify known entities with novel roles in interindividual variance of the response to circulating fatty acids for inflammation biomarkers. Results: A nutrition‐inflammation gene network built from literature and genomics data focusing on Mediterranean diet was compared to a statin‐based network, revealing NR4A2 as a potential subject for genetic analysis. Several NR4A2 variants were associated in the Genetics of Lipid Lowering and Diet Network study with plasma IL6. Using erythrocyte membrane fatty acids (FA) as an exposure, we noted several gene‐environment interactions affecting circulating IL6. Of note, for SNP rs707132 the AA genotype associates with higher IL6 under conditions of high circulating n‐3 PUFA (p=0.016). The rs707132 interaction with erythrocyte n‐3 PUFA on IL6 levels was replicated in the Boston Puerto Rican Health Study (p=0.007). Conclusion Construction of a biological network based on diet, inflammatory markers and cardiometabolic diseases proposed a novel role for transcription factor NR4A2, association with circulating IL6, and interaction with erythrocyte FA status. Funding: NHLBI HL54776/ HL078885, NIH P01AG023394/P50HL105185), USDA contracts 53‐K06‐5‐10/58‐1950‐9‐001.