Dietary Fat Intake Modifies the Effect of a Common Variant in the LIPC Gene on Changes in Serum Lipid Concentrations during a Long-Term Weight-Loss Intervention Trial

Abstract

Background: Hepatic lipase (HL) plays a pivotal role in the metabolism of HDL and LDL. Recent genome-wide association studies have identified common variants in the HL gene (LIPC) associated with HDL cholesterol.

Objective: We tested the effect of a common variant in LIPC on changes in blood lipids in response to weight-loss diets in the Preventing Overweight Using Novel Dietary Strategies Trial.

Methods: We genotyped LIPC rs2070895 in 743 overweight or obese adults aged 30-70 y (61% women) who were assigned to high-fat (40% energy) or low-fat (20% energy) diets for 2 y. We measured serum concentrations of total cholesterol (TC), triglycerides, LDL cholesterol, and HDL cholesterol at baseline and 2 y of intervention.

Results: At 2 y of intervention, dietary fat modified effects of the variant on changes in serum TC, LDL cholesterol, and HDL cholesterol (P-interaction: 0.0008, 0.004, and 0.03, respectively). In the low-fat group, as compared to the G allele, the A allele tended to be related to the decrease in TC and LDL cholesterol concentrations [TC (β ± SE): -5.5 ± 3.0, P = 0.07; LDL cholesterol: -4.8 ± 2.5, P = 0.06] and a lower increase in HDL cholesterol concentrations (β ± SE: -1.37 ± 0.69, P = 0.048), whereas an opposite effect in the high-fat diet group was evident [TC (β ± SE): 7.3 ± 2.7, P = 0.008; LDL cholesterol: 4.1 ± 2.3, P = 0.07], and there was no genetic effect on changes in HDL cholesterol concentrations (P = 0.54).

Conclusion: Dietary fat intake modifies the effect of a common variant in LIPC on changes in serum lipids during a long-term weight-loss intervention in overweight or obese adults. This trial was registered at clinicaltrials.gov as NCT00072995.

Keywords: LIPC; gene-diet interaction; hepatic lipase; high-fat diet; weight-loss intervention.

Conflict of interest statement

Author disclosures: M Xu, SS Ng, GA Bray, DH Ryan, FM Sacks, G Ning, and L Qi, no conflicts of interest.

© 2015 American Society for Nutrition.

Figures

FIGURE 1

Trajectory analysis on 2-y changes in serum total cholesterol (A, D), LDL cholesterol (B, E), and HDL cholesterol (C, F) by LIPC rs2070895 genotype of participants that consumed the low-fat (upper panels) or high-fat (lower panels) diets. The number of participants in the low-fat diet group (A–C), for AA: n = 30 at baseline, n = 22 at 6 mo, and n = 20 at 2 y; AG: n = 138 at baseline, n = 118 at 6 mo, and n = 101 at 2 y; and GG: n = 204 at baseline, n = 182 at 6 mo, and n = 155 at 2 y. The corresponding numbers in the high-fat diet group (D–F), AA: n = 32, 24, and 20, at baseline, 6 mo, and 2 y, respectively; AG: n = 130, 110, and 98, at baseline, 6 mo, and 2 y, respectively; and GG: n = 209,180, and 149, at baseline, 6 mo, and 2 y, respectively. Values are adjusted means ± SEs after adjusting for age, sex, ethnicity, baseline BMI, weight loss, and baseline values for respective outcomes. P-interactions were derived from the linear mixed models, in which intervention time was treated as a repeated measurement factor, and genotype time as the interaction terms. LIPC, hepatic lipase gene.