The G-250A polymorphism in the hepatic lipase gene promoter is associated with changes in hepatic lipase activity and LDL cholesterol: The KANWU Study.
OBJECTIVE
Hepatic lipase (HL) catalyzes the hydrolysis of triglycerides and phospholipids from lipoproteins, and promotes the hepatic uptake of lipoproteins. A common G-250A polymorphism in the promoter of the hepatic lipase gene (LIPC) has been described. The aim was to study the effects of the G-250A polymorphism on HL activity, serum lipid profile and insulin sensitivity.


RESULTS
Altogether 151 healthy subjects (age 49+/-8 years, BMI 26.5+/-3.0kg/m(2)) were randomly assigned for 3 months to an isoenergetic diet containing either a high proportion of saturated fatty acids (SFA diet) or monounsaturated fatty acids (MUFA diet). Within groups there was a second random assignment to supplements with fish oil (3.6g n-3 FA/day) or placebo. At baseline, the A-250A genotype was associated with high serum LDL cholesterol concentration (P=0.030 among three genotypes). On the MUFA diet carriers of the A-250A genotype presented a greater decrease in LDL cholesterol concentration than subjects with other genotypes (P=0.007 among three genotypes). The rare -250A allele was related to low HL activity (P<0.001 among three genotypes). The diet did not affect the levels of HL activity among the genotypes.


CONCLUSIONS
The A-250A genotype of the LIPC gene was associated with high LDL cholesterol concentration, but the MUFA-enriched diet reduced serum LDL cholesterol concentration especially in subjects with the A-250A genotype.
Lindi
Virpi
V
University of Kuopio, Department of Clinical Nutrition, P.O. Box 1627, FIN-70211 Kuopio, Finland.
Schwab
Ursula
U
Louheranta
Anne
A
Vessby
Bengt
B
Hermansen
Kjeld
K
Tapsell
Linda
L
Riccardi
Gabriele
G
Rivellese
Angela A
AA
Laakso
Markku
M
Uusitupa
Matti I J
MI
D000328:Adult; D001315:Australia; D001786:Blood Glucose / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood*; D004041:Dietary Fats / Q000008:administration & dosage*; D005060:Europe; D005227:Fatty Acids / Q000008:administration & dosage; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D008049:Lipase / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D019518:Postprandial Period; D011401:Promoter Regions, Genetic; D013997:Time Factors
D001786:Blood Glucose; D008078:Cholesterol, LDL; D004041:Dietary Fats; D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D005395:Fish Oils; D007328:Insulin; C504173:LIPC protein, human; D008049:Lipase