Lipoprotein lipase gene mutations D9N and N291S in four pedigrees with familial combined hyperlipidaemia
| Autor: | T. W. A. De Bruin, Rachel M. Fisher, H. H. J. J. Van Barlingen, F. Mailly, S. E. Humphries, Philippa J. Talmud, Geesje M. Dallinga-Thie, M. Castro Cabezas |
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| Přispěvatelé: | Other departments |
| Jazyk: | angličtina |
| Rok vydání: | 1996 |
| Předmět: |
Adult
Male Proband medicine.medical_specialty Apolipoprotein B Genetic Linkage Lipolysis Lipoproteins Clinical Biochemistry Population Hyperlipidemia Familial Combined medicine.disease_cause Polymerase Chain Reaction Biochemistry chemistry.chemical_compound Genetic linkage Internal medicine medicine Humans education Gene Alleles Triglycerides Genetics education.field_of_study Mutation Lipoprotein lipase biology Triglyceride Body Weight Nucleic Acid Hybridization nutritional and metabolic diseases General Medicine Middle Aged Pedigree Lipoprotein Lipase Apolipoproteins Cholesterol Phenotype Endocrinology chemistry biology.protein Female lipids (amino acids peptides and proteins) Lod Score |
| Zdroj: | European journal of clinical investigation, 26(8), 631-639. Wiley-Blackwell Karolinska Institutet Scopus-Elsevier |
| ISSN: | 0014-2972 |
| Popis: | The role of the lipoprotein lipase (LPL) gene in familial combined hyperlipidaemia (FCH) is unclear at present. We screened a group of 28 probands with familial combined hyperlipidaemia and a group of 91 population controls for two LPL gene mutations, D9N and N291S. LPL-D9N was found in two probands and one normolipidaemic population control. LPL-N291S was found in four probands and four population controls. Subsequently, two pedigrees from probands with the D9N mutation and two pedigrees from probands with the N291S mutation were studied, representing a total of 24 subjects. Both LPL gene mutations were associated with a significant effect on plasma lipids and apolipoproteins. Presence of the D9N mutation (n = 7) was associated with hypertriglyceridaemia [2 . 69 +/- 1 . 43 (SD) mmol L(-1)] and reduced plasma high-density lipoprotein cholesterol (HDL-C) concentrations (0 . 92 +/- 0 . 21 mmol L(-1)) compared with 11 noncarriers (triglyceride 1 . 75 +/- 0 . 64 mmol L(-1) HDL-C 1 . 23 +/- 0 . 30 mmol L(-1), P = 0 . 03 and P = 0 . 025 respectively). LPL-D9N carriers had higher diastolic blood pressures than non-carriers. LPL-N291S carriers (n = 6) showed significantly higher (26%) apo B plasma concentrations (174 +/- 26 mg dL(-1)) than non-carriers (138 +/- 26 mg dL(-1); P = 0 . 023), with normal post-heparin plasma LPL activities. Linkage analysis revealed no significant relationship between the D9N or N291S LPL gene mutations and the FCH phenotype (hypertriglyceridaemia, hypercholesterolaemia or increased apo B concentrations). It is concluded that the LPL gene did not represent the major single gene causing familial combined hyperlipidaemia in the four pedigrees studied, but that the LPL-D9N and LPL-N291S mutations had significant additional effects on lipid and apolipoprotein phenotype. |
| Databáze: | OpenAIRE |
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