Dietary fat modulation of hepatic lipase variant -514 C/T for lipids: a crossover randomized dietary intervention trial in Caribbean Hispanics

Authors: SMITH, CAREN - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY; VAN ROMPAY, MARIA - TUFTS UNIVERSITY; MATTEI, JOSIEMER - HARVARD UNIVERSITY; GARCIA, J - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY; GARCIA-BAILO, B - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY; LICHTENSTEIN, ALICE - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY; TUCKER, KATHERINE - UNIVERSITY OF MASSACHUSETTS; ORDOVAS, JOSE - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY

Submitted to: Physiological Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/1/2017
Publication Date: 9/22/2017
Citation: Smith, C.E., Van Rompay, M.I., Mattei, J., Garcia, J.F., Garcia-Bailo, B., Lichtenstein, A.H., Tucker, K.L., Ordovas, J.M. 2017. Dietary fat modulation of hepatic lipase variant -514 C/T for lipids: a crossover randomized dietary intervention trial in Caribbean Hispanics. Physiological Genomics. 49(10):592-600. https://doi.org/10.1152/physiolgenomics.00036.2017.
DOI: https://doi.org/10.1152/physiolgenomics.00036.2017

Interpretive Summary: Lipids in the blood, such as high-density lipoprotein, or "good" cholesterol (HDL-C,) influence cardiovascular disease risk. An individual's HDL-C concentration reflects a combination of genetic, dietary and other lifestyle factors. For example, although higher dietary fat will often increase HDL-C, in those with a mutation in hepatic lipase (LIPC,) higher fat is associated with lower HDL-C concentration, which is unfavorable. Support for this gene-diet interaction comes from observational studies, but a higher level of evidence would be provided by a dietary intervention trial. We therefore investigated the LIPC-diet interaction in Caribbean Hispanic individuals using a cross-over intervention design that supplied both a high fat Western diet and a low-fat traditional Hispanic diet. We did not detect a gene-diet interaction according to strict statistical criteria, but we did observe a difference in the HDL-C response to diet that was based on genotype. Briefly, in people lacking the LIPC variant, HDL-C increased in those consuming the high-fat diet, but in those carrying the LIPC variant, the high fat diet did not alter HDL-C. In other words, a high fat diet was neither beneficial nor detrimental to HDL-C in people carrying the LIPC variant. We hypothesize that other factors, such as body weight and insulin resistance, could have influenced HDL-C concentration and made it more difficult to detect a statistically significant gene-diet interaction. This evidence of genetic modulation of dietary responses may inform optimal and personalized dietary fat advice and reinforces the importance of studying genetic markers in diet and cardio-metabolic health.

Technical Abstract: The hepatic lipase (LIPC) locus is a well-established determinant of high-density lipoprotein cholesterol (HDL-C), an association that is modified by dietary fat in observational studies. Dietary interventions are lacking. Methods and Results: We investigated dietary modulation of LIPC rs1800588 (-514 C/T) for lipids and glucose using a randomized cross-over design comparing a high-fat Western diet and a low-fat traditional Hispanic diet in Caribbean Hispanics (n=42; 4 weeks/phase). No significant gene-diet interactions were observed for HDL-C. However, differences in dietary response according to LIPC genotype were observed. In major allele carriers (CC/CT), HDL-C(mmol/L) was higher following the Western diet compared to the Hispanic diet: (Phase 1 (Western:1.3+/-0.04; Hispanic:1.1+/-0.04; P=0.0005). Phase 2 (Western:1.4+/-0.03; Hispanic:1.2+/-0.03; P=0.0003). In contrast, HDL-C in TT individuals did not differ by diet. Only major allele carriers benefited from the higher fat diet for HDL-C. Secondarily, we explored dietary fat quality and rs1800588 for HDL-C and triglyceride (TG) in a Boston Puerto Rican Health Study (BPRHS) subset matched for diabetes and obesity status (subset n=384). In the BPRHS, saturated fat was unfavorably associated with HDL-C and TG in rs1800588 TT carriers. Conclusion: LIPC rs1800588 appears to modify lipids in the context of dietary fat. This new evidence of genetic modulation of dietary responses may inform optimal and personalized dietary fat advice, and reinforces the importance of studying genetic markers in diet and cardio-metabolic health.