Mutations at the Lipoprotein Lipase Gene Locus in Subjects with Diabetes Mellitus, Obesity and Lipaemia

Zhang, Qiuping; Cavallero, E.; Hoffmann, Michael M.; Cavanna, J.; Kay, A.; Charles, Aline; Braschi, Sylvie; März, Winfried; Perlemuter, Léon; Jacotot, B.; Galton, D. J.

doi:10.1042/cs0930335

Cited by 17 publications

(9 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We did not, however, detect LPL gene alterations in patients with mild hypertriglyceridaemia, in agreement with a previous study of diabetic and hypertriglyceridaemic members of Type II diabetic families [42]. In Type II diabetes with severe hypertriglyceridaemia, LPL gene mutations were reported either in isolated cases [9] or in a small group of patients [43]. Lipoprotein lipase activity in plasma after heparin treatment and in adipose tissue is decreased in hypertriglyceridaemic Type II diabetic patients and in insulin-resistant obese subjects [30,44].…”

Section: Discussionsupporting

confidence: 76%

Severe hypertriglyceridaemia in Type II diabetes: involvement of apoC-III Sst-I polymorphism, LPL mutations and apo E3 deficiency

Marçais

Bernard

Merlin³

et al. 2000

Diabetologia

View full text Add to dashboard Cite

Hypertriglyceridaemia and reduced HDL-cholesterol concentrations are the prominent features of the atherogenic dyslipaemia commonly observed in insulin-resistance states [1,2] and Type II (non-insulin-dependent) diabetes mellitus [3±6]. Severe hypertriglyceridaemia is not uncommon in Type II diabetes [7,8] but its prevalence and mechanism are not clearly established. Mild hypertriglyceridaemia in Type II diabetes is dependent upon glucose control and nutritional factors such as intake of carbohydrates and alcohol. Genetic factors might, however, determine individual susceptibility to major hypertriglyceridaemia. Although VLDL hepatic overproduction is well documented in Type II diabetes, genetic defect in the clearance of the triglyceride-rich Diabetologia (2000) Abstract Aims/hypothesis. Hypertriglyceridaemia is common in Type II (non-insulin-dependent) diabetes mellitus. Only subgroups of patient however have type V hyperlipidaemia. To investigate the coordination between genetic factors in the modulation of hypertriglyceridaemia in Type II diabetes, we studied three major modifier loci: apoC-III (both Sst-I and insulinresponsive element polymorphisms), apolipoprotein E genotypes and lipoprotein-lipase mutations. Methods. We studied apoCIII gene polymorphisms, apolipoprotein E genotypes and lipoprotein-lipase gene mutations in 176 patients with Type II (non-insulin-dependent) diabetes mellitus, either normolipaemic (group N, n = 116), mildly hypertriglyceridaemic (group T, n = 28) or with a history of severe hypertriglyceridaemia (triglyceride > 15 g/l) (group H, n = 32). Results. Mild hypertriglyceridaemia in Type II diabetes did not associate with any gene variants in this study. Severe hypertriglyceridaemia was, however, associated with the presence of the apoC-III S2 allele (50 % of the patients in group H compared with 15.5 % in group N, p < 0.0001). Additionally this particular phenotype was associated with a low prevalence of the apo E3 allele (35.9 % in group H vs 18.1 % in group N, p < 0.005) and a statistically significant over-representation of the E2E4 genotypes. Inactivating lipoprotein-lipase mutations were found in four patients (three heterozygotes, one homozygote), none was found in group N or T. Thus 68.7 % of group H patients (22/32) (vs 21.4 % in group T, p < 0.0005) were carriers of either S2 allele, lipoprotein-lipase mutants or E2E4 genotype with most lipoprotein-lipase mutants or E2E4 genotypes or both in the non-carriers for the S2 allele (6/7). Conclusion/interpretation. Our results strongly support the hypothesis that severe hyperlipaemia in Type II diabetes crucially depends on genetic factors which impair the clearance of triglyceride-rich lipoproteins.

show abstract

Section: Discussionsupporting

confidence: 76%

Severe hypertriglyceridaemia in Type II diabetes: involvement of apoC-III Sst-I polymorphism, LPL mutations and apo E3 deficiency

Marçais

Bernard

Merlin³

et al. 2000

Diabetologia

View full text Add to dashboard Cite

show abstract

“…Individual variability in the postprandial lipemic response is usually greater than that observed in the fasting state and it appears to be modulated by environmental and genetic factors (Mero et al 1998). This concept is supported by studies showing that certain polymorphisms at candidate gene loci (the APOA1-APOC3-APOA4 gene complex, APOB, APOE,LIPC,CETP,FABP2 and LPL) are associated with variability in postprandial clearance of lipoprotein (Knudsen et al 1997, Zhang et al 1997, Agren et al 1998, Ostos et al 1998, Fisher et al 1999, Hockey et al 2001, Ordovas 2001.…”

Section: Introductionmentioning

confidence: 56%

Postprandial lipemia is modified by the presence of the polymorphism present in the exon 1 variant at the SR-BI gene locus

Pérez‐Martínez¹,

López‐Miranda²,

Ordovas³

et al. 2004

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

It has recently been reported that carriers of the less common allele at the scavenger receptor class B type I (SR-BI) exon 1 polymorphism are more susceptible to the presence of saturated fatty acid in the diet because of a greater increase in LDL cholesterol. Our aim was to determine if this polymorphism could also influence postprandial lipoprotein metabolism, because the SR-BI has been described as a possible mediator in the intestinal absorption of triacylglycerols. Forty-seven normolipidemic volunteers who were homozygous for the E3 allele at the APOE gene were selected [37 homozygous for the common genotype (1/1) at the SR-BI exon 1 polymorphism and 10 heterozygous (1/2)]. They were given a fat-rich meal containing 1 g fat and 7 mg cholesterol per kg body weight and vitamin A 60 000 IU/m 2 body surface. Fat accounted for 60% of calories, and protein and carbohydrates accounted for 15% and 25% of energy respectively. Blood samples were taken at time 0, every 1 h until 6 h, and every 2·5 h until 11 h. Total cholesterol and triacylglycerols in plasma, and cholesterol, triacylglycerols and retinyl palmitate in triacylglycerol-rich lipoproteins (large and small triacylglycerol-rich lipoproteins) were determined. Postprandial responses for triacylglycerols and retinyl palmitate in small triacylglycerol-rich lipoproteins were higher in 1/1 individuals than in 1/2 individuals. No other significant differences were noted. Our data show that the presence of the genotype 1/2 is associated with a lower postprandial lipemic response.

show abstract

“…Indeed, the possibility that a single nucleotide polymorphism in the promoter region, which impairs the binding of transcription factor Oct-1 and reduces transcription activity to 15% or less, is related to FCHL and ischemic heart disease has been suggested 43) . Reports from Western countries include a study in which LPL gene abnormalities were observed in 10% of patients with type hyperlipoproteinemia 44) , but Arai et al found no LPL gene mutations in any of 100 Japanese subjects with a serum TG level of 400-1,000 mg/dl examined 45) . Generally, poor control of blood glucose in diabetic patients is the most frequent acquired stressor, but drinking, estrogen, steroids, pregnancy, Zoloft (selective serotonin reuptake inhibitor type antidepressant), isotretinoin (treatment for acne), diuretics, -blockers, HIV protease inhibitors, dysproteinemia, multiple myeloma, SLE, malignant lymphoma, etc., have also been reported.…”

Section: Fig 2 Etiological Factors Underlying Primary Type V Hyperlmentioning

confidence: 99%

Diagnosis and Management of Type I and Type V Hyperlipoproteinemia

Gotoda

Shirai

Ohta

et al. 2012

JAT

View full text Add to dashboard Cite

Both type and type hyperlipoproteinemia are characterized by severe hypertriglyceridemia due to an increase in chylomicrons. Type hyperlipoproteinemia is caused by a decisive abnormality of the lipoprotein lipase (LPL)-apolipoprotein C-system, whereas the cause of type hyperlipoproteinemia is more complicated and more closely related to acquired environmental factors. Since the relationship of hypertriglyceridemia with atherosclerosis is not as clear as that of hypercholesterolemia, and since type and hyperlipoproteinemia are relatively rare, few guidelines for their diagnosis and treatment have been established; however, type and hyperlipoproteinemia are clinically important as underlying disorders of acute pancreatitis, and appropriate management is necessary to prevent or treat such complications. Against such a background, here we propose guidelines primarily concerning the diagnosis and management of type and hyperlipoproteinemia in Japanese.

show abstract

Mutations at the Lipoprotein Lipase Gene Locus in Subjects with Diabetes Mellitus, Obesity and Lipaemia

Cited by 17 publications

References 23 publications

Severe hypertriglyceridaemia in Type II diabetes: involvement of apoC-III Sst-I polymorphism, LPL mutations and apo E3 deficiency

Severe hypertriglyceridaemia in Type II diabetes: involvement of apoC-III Sst-I polymorphism, LPL mutations and apo E3 deficiency

Postprandial lipemia is modified by the presence of the polymorphism present in the exon 1 variant at the SR-BI gene locus

Diagnosis and Management of Type I and Type V Hyperlipoproteinemia

Contact Info

Product

Resources

About