Dyslipidemias associated with heterozygous lipoprotein lipase mutations in the French-Canadian population

Julien, Pierre; Gagné, Claude; Murthy, M.R.V.; Lévesque, Georges; Moorjani, Sital; Cadelis, F.; Hayden, Michael R.; Lupien, Paul J.

doi:10.1002/humu.1380110150

Cited by 20 publications

(19 citation statements)

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“…Our results concerning plasma lipids are consistent with findings reported by other investigators [8, 9, 16±18]. The authors of these studies reported that in heterozygous carriers of the Gly188Glu or Pro207Leu mutation expression of hypertriglyceridaemia is dependent on age, obesity and diabetes [8,9,22]. In our study, carriers had significantly higher levels of plasma triglycerides, even after adjustment for age, sex and BMI.…”

Section: Discussionsupporting

confidence: 93%

“…Investigators studied heterozygous carriers of the Gly188Glu mutation and found a significant increase of plasma triglycerides, VLDL cholesterol, and apolipoprotein B (apo B), and a decrease of HDL-and LDL-cholesterol only in a subgroup of individuals over 40 years old [8]. A similar pattern of plasma lipids has been described in heterozygous carriers from French-Canadian families with the Pro207Leu mutation [9]. In a study of 8 heterozygous carriers of the Gly188Glu mutation and 8 control subjects from two families the carriers had clearly reduced LPL activity, but their fasting plasma triglycerides and HDL cholesterol levels were not significantly different from the values of the non-carriers; the carriers had LDL particles of small size and exhibited pronounced postprandial lipemia in a fat tolerance test [10].…”

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confidence: 72%

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Insulin sensitivity is impaired in heterozygous carriers of lipoprotein lipase deficiency

Hölzl¹,

Iglseder

Sandhofer

et al. 2002

Diabetologia

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Section: Discussionsupporting

confidence: 93%

mentioning

confidence: 72%

Insulin sensitivity is impaired in heterozygous carriers of lipoprotein lipase deficiency

Hölzl¹,

Iglseder

Sandhofer

et al. 2002

Diabetologia

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“…LPL is one of the candidate genes of dyslipidemia (Hoffer et al, 1998;Julien et al, 1998;Pillarisetti and Saxena, 2003;Pruneta-Deloche et al, 2005) and hypertension (Williams et al, 1994;Yang et al, 2003b;Li et al, 2004;Chen et al, 2005) because its gene product is a major regulator of triglyceride clearance in the blood. LPL catalyzes the hydrolysis of triglycerides of circulating chylomicrons and VLDL, excesses of which are the potent causes of both disorders.…”

Section: Discussionmentioning

confidence: 99%

Association of lipoprotein lipase (LPL) single nucleotide polymorphisms with type 2 diabetes mellitus

Cho

Han

et al. 2008

Exp Mol Med

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Abbreviations: AUCGLU, glucose area under the curve; AUCINS, insulin area under the curve; BMI, body mass index; DBP, diastolic blood pressure; FDR, false discovery rate; HbA1C, glycosylated hemoglobin; HDLc, high density lipoprotein cholesterol; HOMA-IR, homeostasis model assessment-insulin resistance; LDLc, low density lipoprotein cholesterol; LPL, lipoprotein lipase; SBP, systolic blood pressure; T2DM, type 2 diabetes mellitus; TCHOL, total cholesterol; TG, triglyceride; UTR, untranslated region; WHR, waist hip ratio AbstractThe etiology and pathogenesis of type 2 diabetes mellitus (T2DM) are not completely understood although it is often associated with other conditions such as obesity, hypertension, and dyslipidemia. Lipoprotein lipase (LPL) is a key enzyme in human lipid metabolism that facilitates the removal of triglyceride-rich lipoproteins from the bloodstream. LPL hydrolyzes the core of triglyceride-rich lipoproteins (chylomicrons and very low density lipoprotein) into free fatty acids and monoacylglycerol. To gain insight into the possible role of LPL in T2DM, nine single nucleotide polymorphisms (SNPs) of LPL were analyzed for the association with T2DM using 944 unrelated Koreans, including 474 T2DM subjects and 470 normal healthy controls. Of the nine LPL SNPs we analyzed, a significant association with multiple tests by the false discovery rate (FDR) was observed between T2DM and SNP rs343 (+13836C＞＞＞A in intron 3). SNP rs343 was also marginally associated with some of T2DM-related phenotypes including total cholesterol, high density lipoprotein cholesterol (HDLc), and log transformed glycosylated hemoglobin in 470 normal controls, although no significant association was detected by multiple tests. In total, our results suggest that the control of lipid level by LPL in the bloodstream might be an important factor in T2DM pathogenesis in the Korean population.

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“…8 Indeed, LPL is the enzyme responsible for the hydrolysis of core TG in plasma chylomicrons and very low-density lipoproteins (VLDL), converting TG-rich lipoproteins to intermediate density lipoproteins (IDL) and LDL. 9 LPL also participates in the formation of HDL through this process. Thus, mutations in the LPL gene that alter the activity or mass of the resulting protein may modulate to various extents the metabolism of LDL and HDL particles.…”

Section: Introductionmentioning

confidence: 99%

“…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. 9,14 Other common structural variants in the LPL gene have been shown to have a more modest effect on LPL lipolytic function. 15 One of these mutations, the D9N mutation, has been associated with marginal to substantial increase in plasma TG levels and with an increased risk of coronary artery disease.…”

Section: Introductionmentioning

confidence: 99%

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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Dyslipidemias associated with heterozygous lipoprotein lipase mutations in the French-Canadian population

Cited by 20 publications

References 19 publications

Insulin sensitivity is impaired in heterozygous carriers of lipoprotein lipase deficiency

Insulin sensitivity is impaired in heterozygous carriers of lipoprotein lipase deficiency

Association of lipoprotein lipase (LPL) single nucleotide polymorphisms with type 2 diabetes mellitus

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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