Association of the -514C-->T polymorphism in the hepatic lipase gene (LIPC) promoter with elevated fasting insulin concentrations, but not insulin resistance, in non-diabetic Germans.
Hepatic lipase hydrolyses triglycerides and phospholipids in all major classes of lipoproteins. The -514C-->T genetic variation in the hepatic lipase gene promoter was found to be associated with diminished lipase activity, dyslipidemia, and atherosclerosis. We investigated whether this polymorphism associates with hyperinsulinemia and insulin resistance in 535 normal glucose-tolerant Germans. Only in homozygous individuals (22 subjects), the T allele (frequency: 18.1 %) was significantly associated with elevated glucose concentrations after 120 min of oral glucose tolerance test (p = 0.05) and with elevated fasting concentrations of insulin (p = 0.03), triglycerides (p < 0.01), total and HDL-cholesterol (p = 0.02), as determined by multivariate linear regression analysis. In a recessive model (C/C+C/T vs. T/T), T/T was associated with decreased insulin sensitivity index (p = 0.03) as calculated from oral glucose tolerance test data (n = 535), but not with the glucose infusion rate during hyperinsulinemic euglycemic clamp (n = 218). In conclusion, we have provided evidence that, among the metabolic parameters tested, the hepatic lipase -514C-->T gene polymorphism correlates with elevated fasting insulin concentrations in a German population. Since no corresponding difference in insulin sensitivity was seen in the clamp-subgroup, an effect of this polymorphism on insulin clearance has to be considered.
Machicao
F
F
Department of Endocrinology, Metabolism, and Pathobiochemistry, Medical Clinic Tübingen, Eberhard-Karls-University, Tübingen, Germany.
Staiger
H
H
Fritsche
A
A
Guirguis
A
A
Weisser
M
M
Stumvoll
M
M
Häring
H-U
HU
D000328:Adult; D001161:Arteriosclerosis / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005190:Family; D005215:Fasting; D005260:Female; D005858:Germany; D005951:Glucose Tolerance Test; D006720:Homozygote; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000235:genetics*; D008049:Lipase / Q000235:genetics*; D008297:Male; D008657:Metabolic Clearance Rate; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*
D007328:Insulin; C504173:LIPC protein, human; D008049:Lipase