The Asn-291-->Ser and Ser-477-->Stop mutations of the lipoprotein lipase gene and their significance for lipid metabolism in patients with hypertriglyceridaemia.

We examined 99 Finnish patients whose serum fasting triglycerides (TG) had exceeded 6.0mmol L -1 , with special interest to their lipid, lipoprotein and post-heparin plasma lipase activities. The control group consisted of 75 healthy individuals. We also determined the frequency of the Asn-291→Ser and Ser-447→Stop mutations both in hypertriglyceridaemic (HTG) subjects and in control subjects. A total of 51 of the original 99 hypertriglyceridaemic patients still had TG > 6.0 mmol L -1 when measured a second time. They are referred to as persistently hypertriglyceridaemic subjects (pHTG). The remaining 48 subjects had TG < 6.0 mmol L -1 in the second measurement and are referred to as sporadically hypertriglyceridaemic subjects (sHTG). The allelic frequencies of the Ser-447→Stop mutation in the total HTG and sHTG groups were similar to the frequencies present in the control group, but lower in pHTG patients compared with the control group (0.049 vs. 0.153, X 2 = 6.63, P < 0.05). The Asn-291→Ser mutation was more frequent in HTG group than in the control group (0.0606 vs. 0.013, X 2 = 4.86, P < 0.05). This difference was due to the higher frequency of the minor allele of Asn-291→Ser in the cohort with persistent hypertriglyceridaemia compared with the control group (0.088 vs. 0.013, X 2 = 8.00, P<0.01 ). The highest frequency (0.114) of the minor allele of Asn-29l→Ser was found in type 2 diabetic patients with persistent hypertriglyceridaemia. The carrier status of Asn-291→Ser or Ser-447→Stop did not predict either post-heparin plasma lipoprotein lipase (LPL) activities or lipid and lipoprotein levels in any of the groups studied. Our data suggest that overproduction of very low-density lipoproteins (VLDL) is a more important cause of hypertriglyceridaemia in the Finns than is the LPL deficiency.