A missense mutation (Asp250→Asn) in exon 6 of the human lipoprotein lipase gene causes chylomicronemia in patients of different ancestries

Ma, Yuanhong; Wilson, Bonnie I.; Bijvoet, S.M.; Henderson, Howard; Cramb, Elizabeth; Roederer, Ghislaine O.; Murthy, M.R.V.; Julien, Pierre; Bakker, Henk D.; Kastelein, John J.P.; Brunzell, John D.; Hayden, Michael R.

doi:10.1016/0888-7543(92)90136-g

Cited by 41 publications

(13 citation statements)

References 13 publications

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“…Patient 2 was a compound heterozygote for one novel mutation (Thr101Ala) and a previously described mutation (Asp250Asn). 27 The Thr101Ala mutation disrupted a conserved residue 28 and was associated with low lipoprotein lipase mass and activity in vitro.…”

Section: Patientmentioning

confidence: 99%

Premature Atherosclerosis in Patients with Familial Chylomicronemia Caused by Mutations in the Lipoprotein Lipase Gene

et al. 1996

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Section: Patientmentioning

confidence: 99%

Premature Atherosclerosis in Patients with Familial Chylomicronemia Caused by Mutations in the Lipoprotein Lipase Gene

et al. 1996

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“…5,[11][12][13][14][15][16] The presence of apo CIII-SstI and HL -514 C/T SNPs was identified using the fluorescence polarization detection method. 17 Molecular screening of FH included the detection of nine LDL-receptor gene mutations explaining the majority of cases in the province of Quebec.…”

Section: Genotypingmentioning

confidence: 99%

Genetic epistasis in the VLDL catabolic pathway is associated with deleterious variations on triglyceridemia in obese subjects

et al. 2007

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Background: Abdominal obesity and hypertriglyceridemia (the hypertriglyceridemic-waist phenotype) increase cardiovascular risk. The very low-density lipoprotein (VLDL) is a triglyceride (TG)-rich particle. Frequent variations in the genes coding for enzymes and proteins involved in the VLDL catabolism have already been documented. The epistatic effect of such variants on the risk profile associated with abdominal obesity remains to be elucidated. Objective: This study aims to assess the effect of combinations of frequent single-nucleotide polymorphisms (SNPs) in the VLDL catabolic pathway on the relation between abdominal obesity and fasting TG. Method: Only gene variants in the lipoprotein lipase, apolipoprotein (apo) CIII, hepatic lipase and apo E genes known to be frequent in the general population (allele frequency45%) were included in this study. The presence of selected SNPs was detected by polymerase chain reaction-restriction fragment length polymorphisn in a sample of 640 non-diabetic French Canadians at high cardiovascular risk (405 obese, 235 non-obese). Results: Carrying more than two frequent gene variants involved in the VLDL catabolic pathway significantly increased the risk of hyperTG (odds ratio of TG41.7 mmol/l ¼ 4.15; P ¼ 0.001). This effect was proportional to the number of SNPs and genes involved and was significantly amplified by the presence of abdominal obesity defined on the basis of waist circumference. Conclusion: When combined with abdominal obesity, epistasis in the VLDL pathway has a deleterious effect on fasting TG and coronary artery disease risk profile according to the TG threshold (1.7 mmol/l) used in medical guidelines for the assessment of the metabolic syndrome and associated risk.

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“…Among the numerous mutations responsible for primary LPL deficiency, three missence mutations of the LPL gene (G188E, P207L, D250N) are particularly frequent in the Saguenay-Lac-St-Jean region in the province of Québec in Canada. [10][11][12] The P207L mutation is associated with a carrier frequency of approximately 2% in this population. 13 Heterozygotes carrying these mutations in the LPL gene usually show a deteriorated lipid profile that includes elevated plasma TG levels and decreased HDL cholesterol concentrations.…”

Section: Introductionmentioning

confidence: 97%

Effect of obesity on HDL and LDL particle sizes in carriers of the null P207L or defective D9N mutation in the lipoprotein lipase gene: the Québec LipD Study

et al. 2003

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BACKGROUND:We have recently demonstrated that French Canadians bearing a mutation in the lipoprotein lipase (LPL) gene present an impaired lipoprotein-lipid profile characterized by small low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles compared with healthy subjects. It has also been documented that obesity has a significant impact on HDL and LDL particle sizes. OBJECTIVE: To examine the extent to which obesity modulates HDL and LDL particle sizes among carriers of mutations in the LPL gene. SUBJECTS: Analyses were carried out in 206 heterozygous carriers of the D9N mutation (N ¼ 118) or the P207L mutation (N ¼ 88). MEASUREMENTS: Lipoprotein particle sizes were measured on whole plasma by nondenaturing polyacrylamide gradient gel electrophoresis. RESULTS: In general, body mass index (BMI) and waist circumference were significant correlates of LDL and HDL particle sizes among heterozygous carriers of the P207L or D9N mutation in the LPL gene, with relatively similar associations among men and women. Multivariate analyses indicated that variations in waist circumference but not BMI were an independent predictor of variations in both HDL particle size (5.2%, P ¼ 0.0005) and LDL particle size (5.9%, P ¼ 0.01) in the entire group of heterozygotes for LPL mutation in a model that included the nature of the LPL mutation (D9N vs P207L), gender, age, cholesterol and plasma TG levels. Interestingly, there was a significant interaction between plasma TG levels and waist circumference or BMI in modulating HDL particle size. Indeed, an increased waist circumference or BMI was associated with a significant reduction in HDL particle size among subjects with plasma TG levels r3.5 mmol/l, but not among those with marked hypertriglyceridemia (TG levels 43.5 mmol/l). CONCLUSION: These results suggest that abdominal obesity, more so that overall obesity, is an important determinant of variations in LDL and HDL particle size among heterozygous carriers of mutations in the LPL gene, perhaps further contributing to modulate the risk of CHD in these individuals.

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A missense mutation (Asp250→Asn) in exon 6 of the human lipoprotein lipase gene causes chylomicronemia in patients of different ancestries

Cited by 41 publications

References 13 publications

Premature Atherosclerosis in Patients with Familial Chylomicronemia Caused by Mutations in the Lipoprotein Lipase Gene

Premature Atherosclerosis in Patients with Familial Chylomicronemia Caused by Mutations in the Lipoprotein Lipase Gene

Genetic epistasis in the VLDL catabolic pathway is associated with deleterious variations on triglyceridemia in obese subjects

Effect of obesity on HDL and LDL particle sizes in carriers of the null P207L or defective D9N mutation in the lipoprotein lipase gene: the Québec LipD Study

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