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

Aims Lipoprotein lipase (LPL) is a major regulator of triglyceride clearanc e. A genetic variant of the LPL gene on chromosome 8p22, Asn291Ser, has pre viously been associated with dyslipidaemia and an increased frequency of ca rdiovascular disease as well as familial disorders of lipoprotein metabolis m. The aim of this study was to test whether the phenotypic expression of t he LPL Asn291Ser variant is dependent upon glucose tolerance and insulin re sistance. Therefore, the Asn291Ser variant was examined in 192 patients wit h 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 asses sment (HOMA) index. Results The frequency of the Asn/Ser genotype was significantly increased i n normoglycaemic subjects with hypertriglyceridaemia (> 1.7 mmol/l), and wa s associated with dyslipidaemia and increased systolic blood pressure. Ther e was a significant interaction between Asn291Ser and insulin resistance in normoglycaemic subjects, indicating that dyslipidaemia is more severe in A sn/Ser carriers with reduced insulin sensitivity. The frequency of the Asn/ Ser genotype was not increased in diabetic subjects with hypertriglyceridae mia, but was associated with increased systolic blood pressure. Conclusions The Asn/Ser genotype of the LPL gene is associated with dyslipi daemia in normoglycaemic subjects, and the dyslipidaemic phenotype is more severe in insulin-resistant subjects. This association is not seen in diabe tic subjects.