Interactions between the -514C->T polymorphism of the hepatic lipase gene and lifestyle factors in relation to HDL concentrations among US diabetic men.
BACKGROUND
Low plasma HDL-cholesterol concentrations are a hallmark of diabetic dyslipidemia. A common polymorphism (-514C-->T) of the hepatic lipase gene (LIPC), which accounts for up to 30% of the variation in hepatic lipase activity, has been associated with low hepatic lipase activity and high HDL-cholesterol concentrations.


OBJECTIVE
We examined the association between this polymorphism and plasma HDL-cholesterol concentrations and evaluated whether this association was modified by adiposity and dietary fat intake.


METHODS
We followed men aged 40-75 y who participated in the Health Professionals Follow-Up Study in 1986. Among 18 159 men who returned blood samples by 1994, 780 had confirmed type 2 diabetes at blood drawing or during follow-up to 1998 and were free of cardiovascular disease at blood drawing.


RESULTS
After adjustment for age, smoking, alcohol consumption, fasting status, glycated hemoglobin concentration, physical activity, and body mass index, HDL-cholesterol concentrations were significantly higher in men with the C/T or T/T genotype than in those with the C/C genotype (adjusted x: 40.9 and 38.8 mg/dL, respectively; P = 0.01). We observed significant LIPC -514 polymorphism x body mass index and LIPC -514 polymorphism x saturated fat intake interactions for HDL-cholesterol concentrations (P = 0.003 for both). The T allele was associated with higher HDL-cholesterol concentrations only in men who were not overweight or who had higher saturated fat intake.


CONCLUSIONS
Our study suggests that the effects of -514C-->T of the LIPC gene on HDL concentrations were modified by saturated fat intake and obesity.
Zhang
Cuilin
C
Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA. czhang@hsph.harvard.edu
Lopez-Ridaura
Ruy
R
Rimm
Eric B
EB
Rifai
Nader
N
Hunter
David J
DJ
Hu
Frank B
FB
D000328:Adult; D000368:Aged; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000097:blood* / Q000235:genetics; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D004041:Dietary Fats / Q000008:administration & dosage* / Q000378:metabolism; D015444:Exercise / Q000502:physiology; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000235:genetics; D008019:Life Style; D008049:Lipase / Q000235:genetics*; D008099:Liver / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications* / Q000378:metabolism; D011110:Polymorphism, Genetic; D011446:Prospective Studies
D008076:Cholesterol, HDL; D004041:Dietary Fats; C504173:LIPC protein, human; D008049:Lipase