The expression of type III hyperlipoproteinemia: involvement of lipolysis genes

• Published in: European journal of human genetics : EJHG Vol. 17; no. 5; pp. 620 - 628
• Main Authors: HENNEMAN, Peter, VAN DER SMAN-DE BEER, Femke, SMELT, Augustinus H. M, HANIFI MOGHADDAM, Payman, HUIJTS, Petra, STALENHOEF, Anton F. H, KASTELEIN, John J. P, VAN DUIJN, Cornelia M, HAVEKES, Louis M, FRANTS, Rune R, WILLEMS VAN DIJK, Ko
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.05.2009
• Subjects: Adult; Aged; Aged, 80 and over; Alleles; Apolipoprotein A-V; Apolipoprotein C-III - genetics; Apolipoproteins; Apolipoproteins A - genetics; Biological and medical sciences; Blood Glucose - metabolism; Cardiovascular disease; Cholesterol - blood; Disorders of blood lipids. Hyperlipoproteinemia; DNA Mutational Analysis; Female; Fundamental and applied biological sciences. Psychology; Gene Frequency; Gene polymorphism; General aspects. Genetic counseling; Genetic factors; Genetics of eukaryotes. Biological and molecular evolution; Genotype; Humans; Hyperlipidemia; Hyperlipoproteinemia; Hyperlipoproteinemia Type III - blood; Hyperlipoproteinemia Type III - genetics; Hyperlipoproteinemia Type III - pathology; Hypertriglyceridemia - blood; Hypertriglyceridemia - genetics; Hypertriglyceridemia - pathology; Insulin - blood; Linkage Disequilibrium; Lipase; Lipase - genetics; Lipolysis; Lipolysis - genetics; Lipoprotein lipase; Lipoprotein Lipase - genetics; Liver; Low density lipoprotein; Male; Medical genetics; Medical sciences; Metabolic diseases; Middle Aged; Molecular and cellular biology; Mutation; Netherlands; Polymorphism, Genetic; Rodents; Triglycerides - blood; Netherlands; Enzyme; Metabolic diseases; Lipids; Esterases; Hyperlipoproteinemia; Lipoprotein lipase; Lipoprotein; Gene expression; Lipolysis; Carboxylic ester hydrolases; apoCIII; Gene; Hydrolases; Genetics; type III hyperlipoproteinemia; Single nucleotide polymorphism; Dyslipemia; apoAV; SNP analysis
• ISSN: 1018-4813; 1476-5438
• DOI: 10.1038/ejhg.2008.202

Type III hyperlipoproteinemia (HLP) is mainly found in homozygous apolipoprotein (APO) E2 (R158C) carriers. Genetic factors contributing to the expression of type III HLP were investigated in 113 hyper- and 52 normolipidemic E2/2 subjects, by testing for polymorphisms in APOC3, APOA5, HL (hepatic lipase) and LPL (lipoprotein lipase) genes. In addition, 188 normolipidemic Dutch control panels (NDCP) and 141 hypertriglyceridemic (HTG) patients were genotyped as well. No associations were found for four HL gene polymorphisms and two LPL gene polymorphisms and type III HLP. The frequency of the rare allele of APOC3 3238 G>C and APOA5 -1131 T>C (in linkage disequilibrium) was significantly higher in type III HLP patients when compared with normolipidemic E2/2 subjects, 15.6 vs 6.9% and 15.1 vs 5.8%, respectively, (P<0.05). Furthermore, the frequencies of the APOA5 c.56 G>C polymorphism and LPL c.27 G>A mutation were higher in type III HLP patients, though not significant. Some 58% of the type III HLP patients carried either the APOA5 -1131 T>C, c.56 G>C and/or LPL c.27 G>A mutation as compared to 27% of the normolipidemic APOE2/2 subjects (odds ratio 3.7, 95% confidence interval=1.8-7.5, P<0.0001). The HTG patients showed similar allele frequencies of the APOA5, APOC3 and LPL polymorphisms, whereas the NDCP showed similar allele frequencies as the normolipidemic APOE2/2. Patients with the APOC3 3238 G>C/APOA5 -1131 T>C polymorphism showed a more severe hyperlipidemia than patients without this polymorphism. Polymorphisms in lipolysis genes associate with the expression and severity of type III HLP in APOE2/2.