Interaction between the Asn291Ser variant of the LPL gene and insulin resistance on dyslipidaemia in high risk individuals for Type 2 diabetes mellitus

• Published in: Diabetic medicine Vol. 17; no. 8; pp. 599 - 605
• Main Authors: Klannemark, M., Suurinkeroinen, L., Orho-Melander, M., Groop, L., Taskinen, M. -R.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.08.2000; Blackwell
• Subjects: Aged; Amino Acid Substitution; Apolipoproteins - blood; Asparagine; Biological and medical sciences; Blood Pressure; Cholesterol - blood; Cholesterol, HDL - blood; Chromosomes, Human, Pair 8; Clinical Medicine; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - physiopathology; Diabetes. Impaired glucose tolerance; Disorders of blood lipids. Hyperlipoproteinemia; dyslipidaemia; Endocrine pancreas. Apud cells (diseases); Endocrinology and Diabetes; Endocrinopathies; Endokrinologi och diabetes; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Finland - epidemiology; Gene Frequency; Genetic Variation; Genotype; Homeostasis; Humans; Hyperlipidemias - epidemiology; Hyperlipidemias - genetics; Hypertriglyceridemia - epidemiology; Hypertriglyceridemia - genetics; Insulin Resistance; Klinisk medicin; lipoprotein lipase; Lipoprotein Lipase - genetics; LPL291; Male; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; Metabolic diseases; Middle Aged; Risk Factors; Serine; Triglycerides - blood; Type 2 diabetes mellitus; Finland; Endocrinopathy; Human; Pancreatic hormone; Enzyme; Genetic variant; Metabolic diseases; Lipids; Esterases; Lipoprotein lipase; Non insulin dependent diabetes; Genetic determinism; Insulin; Carboxylic ester hydrolases; Target tissue resistance; Hydrolases; Dyslipemia
• ISSN: 0742-3071; 1464-5491; 1464-5491
• DOI: 10.1046/j.1464-5491.2000.00343.x

SUMMARY Aims   Lipoprotein lipase (LPL) is a major regulator of triglyceride clearance. A genetic variant of the LPL gene on chromosome 8p22, Asn291Ser, has previously been associated with dyslipidaemia and an increased frequency of cardiovascular disease as well as familial disorders of lipoprotein metabolism. The aim of this study was to test whether the phenotypic expression of the LPL Asn291Ser variant is dependent upon glucose tolerance and insulin resistance. Therefore, the Asn291Ser variant was examined in 192 patients with Type 2 diabetes, 278 subjects with normal glucose tolerance who are first degree relatives of patients with Type 2 diabetes and 226 healthy control spouses without family history of diabetes. Methods  The subjects were genotyped with an allele‐specific mini‐sequencing method. Insulin resistance was estimated using the homeostasis model assessment (HOMA) index. Results   The frequency of the Asn/Ser genotype was significantly increased in normoglycaemic subjects with hypertriglyceridaemia (> 1.7 mmol/l), and was associated with dyslipidaemia and increased systolic blood pressure. There was a significant interaction between Asn291Ser and insulin resistance in normoglycaemic subjects, indicating that dyslipidaemia is more severe in Asn/Ser carriers with reduced insulin sensitivity. The frequency of the Asn/Ser genotype was not increased in diabetic subjects with hypertriglyceridaemia, but was associated with increased systolic blood pressure. Conclusions   The Asn/Ser genotype of the LPL gene is associated with dyslipidaemia in normoglycaemic subjects, and the dyslipidaemic phenotype is more severe in insulin‐resistant subjects. This association is not seen in diabetic subjects.