Mutations at the Lipoprotein Lipase Gene Locus in Subjects with Diabetes Mellitus, Obesity and Lipaemia
| Autor: | Sylvie Braschi, Winfried März, Elisabeth Cavallero, Q. Zhang, Bernard Jacotot, Aline Charles, A. Kay, Leon Perlemuter, David J. Galton, Michael M. Hoffmann, J. Cavanna |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Adult
Male medicine.medical_specialty Population Locus (genetics) Biology Diabetes mellitus genetics Insulin resistance Diabetes mellitus Internal medicine Diabetes Mellitus medicine Humans Obesity Allele education Allele frequency Alleles Aged Hypertriglyceridemia education.field_of_study Lipoprotein lipase Exons Sequence Analysis DNA General Medicine Middle Aged medicine.disease Lipoprotein Lipase Endocrinology Mutation Mutagenesis Site-Directed Autoradiography Female |
| Zdroj: | Clinical Science. 93:335-341 |
| ISSN: | 1470-8736 0143-5221 |
| DOI: | 10.1042/cs0930335 |
| Popis: | 1. The common association of obesity, diabetes mellitus and hyperlipidaemia may have a primary aetiological basis. Insulin resistance has been postulated as a possible cause, but defects in the plasma transport of triacylglycerol or fatty acids could also be primary determinants. 2. We have therefore, studied 18 patients with diabetes mellitus, obesity and severe hypertriglyceridaemia for defects of a key protein involved in the clearance of plasma triacylglycerols, lipoprotein lipase. 3. DNA was prepared from leucocytes of 18 patients with the above syndrome, and exons encoding lipoprotein lipase were amplified by PCR. The products were sequenced using the dideoxy chain-termination method. 4. Eight of the subjects were found to possess genetic variants at the lipoprotein lipase gene locus. These were: (a) G579→A, V108V; (b) G818→A, G188E; (c) C829→T, R192; (d) A1127→G, N291S; (e) C1308→G, F351L;(f) C1338→A, T361T; and (g) C1595→G, S447. Three of these, (c), (e) and (f), have not hitherto been described. Variant (f), appears to be a population polymorphism whose allele frequency in normolipidaemic diabetics was found to be 0.12 (162 chromosomes studied). The others are all rare at frequencies of 5. We conclude that genetic variants at the lipoprotein lipase locus occur commonly in subjects with this syndrome (four out of 18 subjects with probably functional mutants) and may affect the individual's response to obesity and diabetes mellitus for the development of lipaemia. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|