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.
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).


CONCLUSIONS
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.
Department of Nutrition, Harvard School of Public Health, Boston, MA; Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai, China; nhlqi@channing.harvard.edu.
Min
M
Xu
Department of Molecular Genetics, GenoVive, New Orleans, LA;
San San
SS
Ng
Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA;
George A
GA
Bray
Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA;
Donna H
DH
Ryan
Department of Nutrition, Harvard School of Public Health, Boston, MA;
Frank M
FM
Sacks
Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai, China; Department of Endocrinology and Metabolism, Ruijin Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China;
Guang
G
Ning
Department of Nutrition, Harvard School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA; and Harvard Medical School, Boston, MA nhlqi@channing.harvard.edu.
Lu
L
Qi
D000328:Adult; D000368:Aged; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood*; D059305:Diet, High-Fat; D004038:Diet, Reducing; D004041:Dietary Fats / Q000008:administration & dosage*; D005260:Female; D055106:Genome-Wide Association Study; D060005:Genotyping Techniques; D006801:Humans; D016014:Linear Models; D008049:Lipase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000178:diet therapy / Q000235:genetics; D050177:Overweight / Q000178:diet therapy / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D014280:Triglycerides / Q000097:blood*; D015431:Weight Loss
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004041:Dietary Fats; C504173:LIPC protein, human; D014280:Triglycerides; D008049:Lipase
LIPC; gene-diet interaction; hepatic lipase; high-fat diet; weight-loss intervention