The Gln-Arg191 polymorphism of the human paraoxonase gene (HUMPONA) is not associated with the risk of coronary artery disease in Finns.

The human paraoxonase gene (HUMPONA) is codominantly expressed as alleles A and G. The A allele codes for glutamine (A genotype) and the G allele for arginine (B genotype) at position 191 of the paraoxonase enzyme. This genetic polymorphism has been suggested to be associated with the predisposition to coronary artery disease (CAD). We investigated the frequency of paraoxonase A and G alleles in 380 well-characterized CAD patients and in 169 controls. The most common genotype in both the patients with CAD (211/380) and in healthy Finnish individuals (87/169) was AA (Gln/Gln). The heterozygous AM (Gln/Arg) genotype was present in 140 of the patients and in 75 controls. The frequency of the A allele was 0.74 in both patients and controls. The genotype distribution between the two groups did not differ (P = 0.12, chi2 test). The genotype distributions were also similar to those reported earlier in other caucasoid populations. In conclusion, we found no association between the Gln-Arg 191 polymorphism of the human paraoxonase gene and coronary artery disease in Finns.

Association of variation in hepatic lipase activity with promoter variation in the hepatic lipase gene. The LOCAT Study Invsestigators.

The associations between six genetic polymorphisms in the hepatic lipase (HL) gene (LIPC) and variation in postheparin HL activity and fasting serum lipoproteins were evaluated in 395 male Finnish coronary heart disease patients with HDL cholesterol concentrations

Immunolocalization of Antifreeze Proteins in Winter Rye Leaves, Crowns, and Roots by Tissue Printing.

During cold acclimation, antifreeze proteins (AFPs) that are similar to pathogenesis-related proteins accumulate in the apoplast of winter rye (Secale cereale L. cv Musketeer) leaves. AFPs have the ability to modify the growth of ice. To elucidate the role of AFPs in the freezing process, they were assayed and immunolocalized in winter rye leaves, crowns, and roots. Each of the total soluble protein extracts from cold-acclimated rye leaves, crowns, and roots exhibited antifreeze activity, whereas no antifreeze activity was observed in extracts from nonacclimated rye plants. Antibodies raised against three apoplastic rye AFPs, corresponding to a glucanase-like protein (GLP, 32 kD), a chitinase-like protein (CLP, 35 kD), and a thaumatin-like protein (TLP, 25 kD), were used in tissue printing to show that the AFPs are localized in the epidermis and in cells surrounding intercellular spaces in cold-acclimated plants. Although GLPs, CLPs, and TLPs were present in nonacclimated plants, they were found in different locations and did not exhibit antifreeze activity, which suggests that different isoforms of pathogenesis-related proteins are produced at low temperature. The location of rye AFPs may prevent secondary nucleation of cells by epiphytic ice or by ice propagating through the xylem. The distributions of pathogenesis-induced and cold-accumulated GLPs, CLPs, and TLPs are similar and may reflect the common pathways by which both pathogens and ice enter and propagate through plant tissues.

Heterozygous hepatic lipase deficiency, due to two missense mutations R186H and L334F, in the HL gene.

Hepatic lipase (HL) is an endothelial enzyme involved in the metabolism of intermediate density lipoproteins (IDL) and high density lipoproteins (HDL) in plasma. In a Finnish pedigree consisting of 18 members belonging to three generations two missense mutations RI86H and L334F in exons 5 and 7 of the HL gene co-segregated with low post-heparin HL activity. Haplotype analysis of the HL gene in family members revealed a high degree of genetic variation and demonstrated that the two missense mutations reside on the same chromosome. In vitro site-directed mutagenesis and expression of the cDNA constructs in COS-1 cells revealed that the R186H mutation leads to a protein that is not secreted while the L334F mutation results in the production of a HL protein that is secreted but has only about 30% of wild type HL activity. Carriers of the mutated HL gene exhibited clearly reduced HL activity and mass in post-heparin plasma. Probably due to their heterozygous carrier status they had only moderate elevation of total triglycerides, IDL, and LDL-triglycerides. The LDL-particles were enriched in triglycerides and depleted of cholesterol. Also their HDL2- and HDL3-particles were enriched in triglycerides.

Phenotype expression in familial combined hyperlipidemia.

Familial combined hyperlipidaemia (FCHL) is one of the most common hereditary disorders predisposing to early coronary death. The affected family members have elevations of serum total cholesterol, triglycerides or both. Despite intensive research efforts the genetic and metabolic defects underlying this complex disorder are still unknown. To dissect the metabolism and genetics of FCHL the phenotype of an individual must be precisely defined. We assessed the influence of different diagnostic criteria on the phenotype definition and studied factors affecting the phenotype expression in 16 large Finnish families (n = 255) with FCHL. The fractile cut-points used to define abnormal lipid values had a profound influence on the diagnosis of FCHL. If the 90th percentile cut-point was used, approximately 45% of the family members were affected, in concord with the presumed dominant mode of transmission for FCHL. If the 95th percentile was used only 22% of study subjects were affected. To characterize the metabolic differences or similarities between the different lipid phenotypes, we determined very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) particles separated by ultracentrifugation. In linkage analysis no single ultracentrifugation variable could discriminate reliably affected family members from non-affected family members. Our data emphasizes the need for re-evaluation of FCHL diagnostic criteria. Preferably, the diagnosis should be based on a single, reliable metabolic marker.

Pathology of renal arteries of dyslipidemic children with congenital nephrosis.

Congenital nephrotic syndrome of the Finnish type (CNF) is well characterized in infants and associated with major lipid risk factors for atherosclerosis. This study was undertaken to investigate if any arterial pathology is present in children with CNF and, if so, to describe its nature in renal arteries collected at nephrectomy at a mean age of 12.5 +/- 4.4 months. Denuded endothelial injury and intimal thickening were seen in 9 out of 10 patient specimens of renal arteries. Intimal thickening contained loose abundant extracellular matrix with a few smooth muscle or myofibroblastoid cells. Only a few Sudan black- or oil red O-positive lipid droplets were found in six and seven samples, respectively. Areas immunoreactive with antibodies against apoprotein B were seen in only two specimens. Immunohistochemistry did not reveal any activated T or B cells, or any expression of IL-1 or IL-2 receptors. Macrophages were present in only two specimens. No foam cells were seen. We conclude that the vascular pathology together with altered lipoprotein metabolism indicates that children with CNF might be at risk for early atherosclerotic arterial disease, particularly if their hyperlipidemia persists.

Skeletal muscle protein mass correlates with the lipid status in children with solid tumors and before bone marrow transplantation.

OBJECTIVE: To evaluate the changes in lipid status in children during anticancer therapy, with special reference to the effect of protein-energy malnutrition on plasma lipids. DESIGN: Prospective follow-up study. SETTING: The study was carried out in the Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland SUBJECTS: The study group consisted of 33 children going through bone marrow transplantation (BMT) and 10 children with malignant solid tumors. The BMT patients were evaluated before transplantation and 1 and 3 months after BMT, and the tumor patients were studied at diagnosis and in remission. The reference group consisted of 23 healthy children. INTERVENTIONS: As indicators of lipid status, lipoproteins and the concentration of cholesterol and triacylglycerol were measured. Protein reserves were expressed as muscle index (MI), derived from ultrasonographic measurement of the femoral quadriceps muscle. Body weight, triceps skinfold thickness and the serum concentration of albumin, prealbumin and transferrin were measured. RESULTS: In both groups, plasma concentration of total triacylglycerol was increased and high-density lipoprotein (HDL) cholesterol decreased as compared to the reference subjects. Plasma triacylglycerol concentration had a negative correlation with skeletal muscle protein mass (MI; r=0.34, P=0.02). The concentration of serum prealbumin correlated positively with plasma total cholesterol concentration (r=0.47, P=0.002). CONCLUSIONS: In children with cancer, abnormalities of lipid status are associated with changes in skeletal muscle protein reserves. SPONSORSHIP: This study was supported by the Foundation of Pediatric Research, Helsinki, Finland and the Nona and Kullervo Väre Foundation, Helsinki, Finland.

Short-term effects of renal transplantation on plasma lipids and lipoprotein lipase in children with congenital nephrosis.

Plasma lipoprotein and apoprotein (apo) A-I, A-II and B concentrations and post-heparin plasma lipoprotein lipase (LPL) activity and mass were measured in 13 children with congenital nephrotic syndrome of the Finnish type (CNF) six months after renal transplantation to determine whether the severe lipid abnormalities documented prior to and during peritoneal dialysis would normalize. Plasma total triglyceride decreased by 52% (p < 0.001), VLDL triglyceride by 55% (p < 0.01) and total cholesterol by 17% (p < 0.01). HDL cholesterol increased by 51% (p < 0.001), whereas no significant change was observed in LDL cholesterol. Despite these improvements, plasma lipoprotein concentrations were still abnormal after transplantation. Total (p < 0.01) and VLDL triglyceride (p < 0.05) as well as total (p < 0.01), VLDL (p < 0.01) and LDL cholesterol (p < 0.01) were higher than in control children. HDL cholesterol normalized. Plasma apo A-I and A-II concentrations were normal, but the apo B concentration remained high (p < 0.01). Post-heparin LPL activity and mass were normal (25.0 +/- 9.1 mumol FFA/ml/h and 227.2 +/- 88.4 ng/ml). The mean cyclosporine dose correlated positively with the serum creatinine concentration (r = +0.72, p < 0.01). Positive correlations were also observed between total (r = +0.68, p < 0.05) and VLDL triglyceride (r = +0.62, p < 0.05) and the serum creatinine concentrations. We conclude that renal transplantation substantially improves the triglyceride and cholesterol abnormalities in CNF but significant abnormalities still persist.

Growth, serum lipoproteins and apoproteins in infants with congenital nephrosis.

Retarded growth and extremely high cholesterol levels have been reported in infants with congenital nephrotic syndrome of the Finnish type (CNF). In an attempt to normalize growth and lipid disturbances the high-calorie diet (130 kcal/kg/d) containing protein 4 g/kg/d and supplemented with unsaturated fatty acids (mean P/S-ratio 1.40) was given to ten infants with CNF from birth. Growth, lipoprotein and apoprotein concentrations were measured. All patients exhibited normal growth, which allows renal transplantation, the only life-saving treatment in CNF, already at an early age. In spite of the diet lipid profiles at 3 and 9 months revealed marked elevation of triglyceride in all lipoproteins, especially in VLDL fraction, compared to controls. The abnormalities increased significantly with time (p for VLDL-TG 0.04). The elevation of serum cholesterol was mainly attributable to the increase of cholesterol in triglyceride-rich particles (chylomicrons, VLDL, IDL). Analysis of VLDL, LDL and HDL revealed significant triglyceride enrichment and cholesterol deficiency in all lipoproteins. The concentrations of the low-molecular weight apoproteins A-I and A-II were significantly decreased, but the concentration of high-molecular apo B was high. Urinary analysis revealed progression and decreasing selectivity of proteinuria with time. Thus the mechanisms leading to lipid abnormalities in CNF are multiple including stimulated hepatic lipoprotein synthesis, impaired conversion of VLDL and IDL to LDL, compositional changes, urinary loss of low-molecular apoproteins and presumably reduced LPL activity. The abnormalities indicate an increased risk of arteriosclerosis in CNF patients.

Peritoneal dialysis in children under 5 years of age.

OBJECTIVE: We report our experience with maintenance peritoneal dialysis (PD) in small children. DESIGN: This is a retrospective analysis of the patient records of all children under the age of 5 years treated with continuous peritoneal dialysis (CPD) between 1986 and 1994 in Finland. SETTING: Treatment was started and the patients were seen at the outpatient clinic at the Hospital for Children and Adolescents, University of Helsinki, every 3 months. Between these visits, they had controls at their local hospital every 2-4 weeks. PATIENTS: The most common primary renal disease in these 34 patients was congenital nephrotic syndrome of the Finnish type (27 patients). Others were: congenital nephrotic syndrome (3 patients), polycystic kidney disease (1), urethral valve (1), neuroblastoma (1), and renal dysplasia (1). RESULTS: Mean age at onset was 1.6 years and median treatment time 9.3 months. Time spent in hospital decreased from 270 days/year in the 1980s to 150 days/year in the 1990s. Two children died (5.9%). The peritonitis rate on continuous cyclic peritoneal dialysis was 1:11.5 patient-months. Hernias were diagnosed in 29% of the patients. After 3 months half of the patients were on antihypertensive medication. Pulmonary edema was diagnosed once in 12 patients and twice in 2 patients. During the first 6 months on PD the mean height standard deviation score (hSDS) increased from -2.13 to -1.66 (p < 0.0001). The 6-month change in hSDS before initiation and 6 months after the start of CPD increased from -0.12 +/-0.68 to +0.59 +/- 0.64 (p = 0.0008). CONCLUSIONS: Our results indicate that peritoneal dialysis is feasible and safe in small children. Mortality was low and growth was good. The major challenges presented by CPD therapy were maintenance of optimal nutrition, avoidance of peritonitis, and control of volemia.

Carotid intima-media thickness after pediatric renal or liver transplantation at high-resolution B-mode ultrasonography.

In a previous study, we observed a higher incidence of dyslipidemia in pediatric renal recipients compared with liver recipients. In the present study, we measured common carotid artery intima-media thickness (IMT) in 13 pediatric renal recipients, 9 liver recipients, and 26 control individuals with median age of 11.4, 10.8, and 12.0 years, respectively. The patients were studied from 0.2 to 10.8 years after renal transplantation (RTx) or liver transplantation (LTx). An experienced radiologist (T.K.) blinded to the status of the children measured the IMT using a high-resolution B-mode ultrasonography method. In patients who underwent RTx or LTx, serum fasting lipid profile, estimates of renal and liver function, and glucose metabolism were determined. Children undergoing RTx or LTx more often had hypertension compared with the control individuals (P = .004). Before transplantation, dyslipidemia was greater in patients undergoing RTx compared with those undergoing LTx (P < .05). Children who underwent RTx, compared with those who underwent LTx or control individuals, had thicker mean IMT at the 6 sites measured (mean [SD], 0.57 [0.07], 0.51 [0.05], and 0.53 [0.06] mm, respectively; P = .02]. As a result of linear regression in renal recipients, variability of glomerular filtration rate (<60 mL/min/1.73 m(2) vs normal) accounted for 43.3% of variability of the mean of maximal IMT (B = 8.9; SE = 3.1; P = .01). Variability of pre-RTx serum triglyceride concentration (B = 1.6; SE = 0.6; P = .03) and actual triglyceride concentration (B = 10.3; SE = 2.2; P = .002) accounted for 82.2% of variability of maximal IMT. Our findings support previous data on the importance of maintenance of good graft function with sufficient but not overly efficient immunosuppression after transplantation in prevention of future cardiovascular disease.

Protein and lipid metabolism in nephrotic infants on peritoneal dialysis after nephrectomy.

Congenital nephrotic syndrome of the Finnish type (CNF) is associated with protein deficiency despite substantial protein supplementation in the nephrotic state before nephrectomy. Different protein intakes (2.5 vs. 3.7 g/kg per day) in hypoproteinaemic children on continuous cycling peritoneal dialysis (CCPD) were studied. Lipids were also measured to determine whether severe atherogenic abnormalities seen during nephrosis improved after nephrectomy. Growth was normal or became normal with both protein intakes. Serum pre-albumin and transferrin concentrations became normal. Total protein (57 +/- 3.0 vs. reference limits 60-75 g/l) and albumin (28 +/- 5.0 vs. reference limits 30-50 g/l) concentrations improved but remained below normal, even with the higher protein intake. Muscle mass determined by measuring femoral quadriceps muscle thickness using ultrasound was markedly reduced in all patients at nephrectomy. It improved (P < 0.05) in all but 2 patients who had several bacterial infections, but reached normal level in only 3 patients within 6 months. Plasma total, very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) triglyceride concentrations decreased (P < 0.05, P < 0.05 and P < 0.01, respectively) and VLDL, LDL and high-density lipoprotein (HDL) particles contained less triglyceride than in the nephrotic state. HDL cholesterol concentrations increased by 28% [0.58 +/- 0.22 mmol/l during nephrosis, 0.81 +/- 0.21 mmol/l on CCPD after nephrectomy (P < 0.05)] but remained below the level of 1.38 +/- 0.75 mmol/l in normal controls (P < 0.001). If compared with controls there were still significant abnormalities in lipoprotein concentrations on CCPD.(ABSTRACT TRUNCATED AT 250 WORDS)

Management of congenital nephrotic syndrome of the Finnish type.

Congenital nephrotic syndrome of the Finnish type (CNF) is a rare autosomal recessively inherited disease characterised by intrauterine onset of massive urinary loss of proteins, 90% of which is albumin. The CNF gene has been localised to the long arm of chromosome 19, but the pathogenesis remains unclear. Historically, all CNF patients died, usually within the first 6 months of life. Today, a normal life can be achieved for a child with CNF by correcting the protein deficiency and normalising nutrition. This is accomplished by early intravenous albumin supplementation, nutritional support, aggressive treatment of complications and early renal transplantation, after bilateral nephrectomy and peritoneal dialysis. In the present article current treatment strategies are reviewed, and our own experience with 43 CNF patients during the last 10 years is presented.

A novel amino acid substitution (His183-->Gln) in exon 5 of the lipoprotein lipase gene results in loss of catalytic activity: phenotypic expression of the mutant gene in a heterozygous state.

We have identified a hitherto unrecognized mutation of the lipoprotein lipase gene (LPL) in a Finnish family with Russian and Swiss ancestors. A single base pair substitution of a guanine for cytosine in codon 183 of exon 5 of the LPL gene results in a change of histidine to glutamine in the mature enzyme protein. Expression of a mutant cDNA construct in COS cells resulted in secretion of inactive LPL enzyme protein confirming the functional significance of the mutation. The proband, a 50-year-old female and her two daughters were all heterozygous for the His183-->Gln mutation. Clinically, the proband was characterized by variable and occasionally severe hypertriglyceridemia, obesity, hypertension, coronary heart disease and non-insulin-dependent diabetes mellitus. The daughters, aged 24 and 19 years, were also obese but had milder hypertriglyceridemia. In conclusion, we have identified a novel LPL mutation that results in the synthesis of an inactive enzyme protein. Although the assessment of a causative link between the mutation and hyperlipidemia awaits further studies, our data suggest that heterozygosity for a functional defect of LPL should be considered in patients presenting with the metabolic dyslipidemic syndrome, "syndrome-X."

Development and evaluation of an ELISA method for the determination of lipoprotein lipase mass concentration--comparison with a commercial, one-step enzyme immunoassay.

We developed a non-competitive, enzyme-linked, immunosorbent assay (ELISA) for the quantitation of lipoprotein lipase (LPL) in human postheparin plasma using affinity-purified antihuman milk lipoprotein lipase antibodies produced in chicken eggs and a monoclonal antibody directed against human lipoprotein lipase. We compared our ELISA method with a commercially available sandwich-enzyme immunoassay (Markit-F LPL EIA Kit, Dainippon Pharmaceutical Co, Ltd. Osaka, Japan). The reference values for lipoprotein lipase catalytic activity concentration and mass concentration in healthy Finns were determined. Lipoprotein lipase activity concentration (mean +/- SD) was 297 +/- 112 U/l in women, and mass concentration as measured by the ELISA method was 1058 +/- 367 micrograms/l. The corresponding values for men were 247 +/- 97 U/l and 815 +/- 207 micrograms/l, respectively. Across the whole concentration range of the ELISA method, the control samples' intra- and inter-assay coefficients of variation (CV) were 5.1% and 6.5%, respectively. The correlation between the ELISA and EIA methods was good, r = +0.81. The importance of the correct standardisation of immunoassays is discussed.

Hepatic lipase gene polymorphisms influence plasma HDL levels. Results from Finnish EARS participants. European Atherosclerosis Research Study.

Hepatic lipase (HL), a triglyceride lipase found in liver, adrenals, testes, and ovaries, takes part in the uptake, remodeling, and function of lipoproteins including HDL, as well as VLDL and chylomicrons. In the present study, the genotype distribution of five HL polymorphisms (-C480T, V133V, T202T, L334F, T457T) and their association to plasma lipid values were investigated. The study participants included 92 students with paternal history of myocardial infarction before the age of 55 and 194 matched control subjects, ie, the Finnish participants of the European Atherosclerosis Research Study (EARS). The allele T of the HL polymorphism -C480T showed an association with elevated HDL, apoA-I, and LpA-I values (ANOVA P < .01). No difference in genotype distribution was observed in the offspring with and without paternal history of myocardial infarction.

Factors limiting the erythropoietin response in rapidly growing infants with congenital nephrosis on a peritoneal dialysis regimen after nephrectomy.

To prevent anemia in seven small children with congenital nephrotic syndrome of the Finnish type (age range 1 to 4 years), we gave recombinant human erythropoietin in a dose up to 150 IU/kg/per week. We then studied the limiting factors during 14 weeks. On a peritoneal dialysis regimen after nephrectomy, the patients grew considerably (range +0.1 to 2.2 kg/14 wk; mean + 1.3 kg/14 wk). The amount of blood taken for laboratory studies was estimated. Although the estimated erythrocyte volume increased, the improvement was masked in most patients by enhanced growth. In two patients the target hemoglobin value of 10 gm/dl was reached, and in three patients transfusions were avoided. The reticulocyte count rose in dose-dependent fashion. In five patients protein malnutrition was not prevented, although intake of protein was as recommended. The gradual decrease in serum ferritin values indicated that mobilization of iron stores was adequate. Serum iron values decreased, although in general remaining within normal limits. In six patients the serum copper concentration was low and in two the serum aluminum concentration was slightly elevated. Two patients had several episodes of infection. We conclude that in rapidly growing infants and small children receiving peritoneal dialysis after nephrectomy, the maintenance or elevation of the hemoglobin concentration depends on several limiting and coinciding factors. We speculate that, when protein is limited, body growth has priority over erythropoiesis. A higher dose of erythropoietin might have evoked a better response in hemoglobin concentration but might also have resulted in progression of the protein deficit.

Changes in biological activity and immunoreactive mass of lipoprotein lipase in congenital nephrosis: relationship to hypertriglyceridaemia.

The major lipid disturbance in children with congenital nephrosis of the Finnish type (CNF) is hypertriglyceridaemia. To determine whether or not hypertriglyceridaemia is caused by defective triglyceride catabolism, we measured lipoprotein lipase (LPL) activities and masses at various stages of the disease. At age 3 months in CNF both LPL activity and mass were decreased, but a close positive correlation between these parameters similar to that in controls was observed. At age 9 months both LPL activity and mass were even lower. At that time a significant positive correlation (r = 0.72, P < 0.05) between LPL activities and albumin concentrations and significant negative correlations between plasma free fatty acid (FFA) concentrations and LPL activities (r = -0.72, P < 0.05) and between plasma FFA concentrations and serum albumin concentrations (r = -0.73, P < 0.05) were observed, suggesting that low albumin concentrations result in increase of FFA levels, which could interfere with a normal LPL function at the endothelial surface. On dialysis after nephrectomy, LPL activities and masses increased. At age 3 and 9 months apoprotein C-II (apo C-II) and apoprotein C-III (apo C-III) levels were not decreased although apoproteins were being lost into the urine. On dialysis the mean ratio of apo C-II/C-III was significantly lower than the mean in controls (P < 0.001). We conclude that impaired function of LPL seems to be the major cause of hypertriglyceridaemia and disintegrity of the VLDL-IDL-LDL delipidation cascade in children with CNF.

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 6.0 mmol 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, chi(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, chi(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, chi(2) = 8.00, P < 0.01). The highest frequency (0.114) of the minor allele of Asn-291-->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.