Interaction between the Asn291Ser variant of the LPL gene and insulin resistance on dyslipidaemia in high risk individuals for Type 2 diabetes mellitus.
OBJECTIVE
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/1), 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.
Klannemark
M
M
Department of Endocrinology, Malmö University Hospital, University of Lund, Sweden. mia.klannemark@endo.mas.lu.se
Suurinkeroinen
L
L
Orho-Melander
M
M
Groop
L
L
Taskinen
M R
MR
D000368:Aged; D019943:Amino Acid Substitution; D001053:Apolipoproteins / Q000097:blood; D001216:Asparagine; D001794:Blood Pressure; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D002898:Chromosomes, Human, Pair 8; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D005387:Finland / Q000453:epidemiology; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006706:Homeostasis; D006801:Humans; D006949:Hyperlipidemias / Q000453:epidemiology* / Q000235:genetics; D015228:Hypertriglyceridemia / Q000453:epidemiology / Q000235:genetics; D007333:Insulin Resistance; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012694:Serine; D014280:Triglycerides / Q000097:blood
D001053:Apolipoproteins; D008076:Cholesterol, HDL; D014280:Triglycerides; D012694:Serine; D001216:Asparagine; D002784:Cholesterol; D008071:Lipoprotein Lipase