The Asp
            <sub>9</sub>
            Asn Mutation in the Lipoprotein Lipase Gene Is Associated With Increased Progression of Coronary Atherosclerosis

Jukema, J. Wouter; Boven, Ad J. van; Groenemeijer, Björn E.; Zwinderman, Aeilko H.; Reiber, J. H. C.; Bruschke, Albert V.G.; Henneman, J. A.; Molhoek, G. P.; Bruin, T.; Jansen, Hans; Gagné, Éric; Hayden, Michael R.; Kastelein, John J.P.

doi:10.1161/01.cir.94.8.1913

Cited by 113 publications

(60 citation statements)

References 17 publications

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“…The REGRESS study found that the D9N variant in LPL attenuated the total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) response to pravastatin, but had no significant effect on angiographic progression of coronary artery lesions. 13 In our initial studies in the Post-Coronary Artery Bypass Graft Trial (Post-CABG Trial) cohort, we observed no effect of D9N, whereas the HindIII variant in LPL was associated with increased coronary graft narrowing over time, independent of the degree of lipid lowering (moderate versus aggressive) with lovastatin. 14,15 In this study, we expand on the latter result, examining the association of LPL haplotypes with the atherosclerosis and lipid response to lovastatin therapy.…”

Section: Introductionmentioning

confidence: 85%

Haplotypes in the lipoprotein lipase gene influence high-density lipoprotein cholesterol response to statin therapy and progression of atherosclerosis in coronary artery bypass grafts

et al. 2006

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Lipoprotein lipase (LPL) hydrolyzes circulating triglycerides (TGs). We previously showed that 3 0 -end haplotypes in the LPL gene influence atherosclerosis and insulin resistance. This study asked whether these LPL haplotypes influence response to lipid-lowering therapy among 829 subjects from the Post-Coronary Artery Bypass Graft trial. Lipid profiles were obtained at baseline and 4-5 years after treatment with lovastatin. Haplotypes were based on 12 SNPs. The fourth most frequent haplotype, 12-4, was associated with a decreased increment in high-density lipoprotein-cholesterol (HDL-C) following treatment. Haplotypes 12-6, 12-7 and 12-8 were each associated with increased HDL-C response to therapy, and haplotype 12-2 with decreased TG response. The most common haplotype, 12-1, was protective against graft worsening or occlusion. Haplotype 12-4 reduced HDL-C response to lovastatin, possibly consistent with our prior observations of this haplotype as predisposing to coronary artery disease. LPL may influence atherosclerosis risk through pleiotropic effects on each aspect of the metabolic syndrome.

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Section: Introductionmentioning

confidence: 85%

Haplotypes in the lipoprotein lipase gene influence high-density lipoprotein cholesterol response to statin therapy and progression of atherosclerosis in coronary artery bypass grafts

et al. 2006

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“…Moreover, it has been reported that the elevated triglyceride level characteristic of familial LPL deficiency is associated with premature atherosclerosis (17). It has also been reported that mutations in the LPL gene that are not associated with complete LPL deficiency nonetheless increase the risk of ischemic heart disease (18) and progression of CAD (19). Finally, it has been reported that LPL activity is inversely related to the severity of angina pectoris in patients with CAD (20).…”

Section: Discussionmentioning

confidence: 99%

Autoantibodies to lipoprotein lipase and dyslipidemia in systemic lupus erythematosus

Reichlin

Fesmire

Quintero-Del-Rio

et al. 2002

Arthritis & Rheumatism

115

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Objective. To demonstrate the binding of bovine lipoprotein lipase (LPL) by IgG from sera obtained from patients with systemic lupus erythematosus (SLE) and other rheumatic diseases, and the relationship of anti-LPL to triglyceride levels in SLE.Method. Binding of LPL by IgG from sera obtained from patients with SLE and other rheumatic diseases was measured by an enzyme-linked immunosorbent assay technique. Lipid profiles for fasting blood samples obtained from SLE patients and control subjects were determined.Results. Sera obtained from 105 patients with SLE were assessed for reactivity with LPL, and 49 (47%) of the results were positive. Sera obtained from patients with rheumatoid arthritis (RA) (n ‫؍‬ 80), Sjögren's syndrome (n ‫؍‬ 30), polymyositis and dermatomyositis (n ‫؍‬ 30), and progressive systemic sclerosis (n ‫؍‬ 31) were also studied, and 10 (13%), 3 (10%), 12 (40%), and 13 (42%), respectively, were positive for reactivity with LPL. It was determined that all affinity-purified antidouble-stranded DNA (dsDNA) antibodies and 4 of 5 monoclonal anti-dsDNA antibodies bound to LPL. The binding of IgG depleted of anti-dsDNA to LPL indicates a second anti-LPL activity in SLE. Measurements of fasting lipid levels in SLE patients with anti-LPL revealed a strong positive correlation of antibody levels and total serum triglycerides, apolipoprotein B, and apolipoprotein E concentrations.Conclusion. Antibodies to LPL occurred in 47% of SLE patients and in a similar percentage of patients with polymyositis or systemic sclerosis. The prevalence of these antibodies was less in patients with RA or Sjögren's syndrome. It is hypothesized that the elevated triglyceride levels in SLE patients are in part attributable to anti-LPL, and this lipid abnormality could contribute to the premature atherosclerosis known to be present in patients with SLE.

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“…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. [16][17][18] The D9N mutation underlies heterozygosity for LPL deficiency in 2-5% of Caucasians. 18,19 We have recently demonstrated that individuals bearing a mutation in the LPL gene presented small LDL and HDL particles compared with healthy subjects and that carriers of the P207L mutation in the LPL gene were characterized by smaller LDL particles than carriers of the D9N mutation.…”

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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The Asp ₉ Asn Mutation in the Lipoprotein Lipase Gene Is Associated With Increased Progression of Coronary Atherosclerosis

Abstract: This study shows that heterozygosity for a mutation in the LPL gene, which causes only subtle changes in fasting plasma lipids, may promote the progression of coronary atherosclerosis and diminish clinical event-free survival.

Cited by 113 publications

References 17 publications

Haplotypes in the lipoprotein lipase gene influence high-density lipoprotein cholesterol response to statin therapy and progression of atherosclerosis in coronary artery bypass grafts

Haplotypes in the lipoprotein lipase gene influence high-density lipoprotein cholesterol response to statin therapy and progression of atherosclerosis in coronary artery bypass grafts

Autoantibodies to lipoprotein lipase and dyslipidemia in systemic lupus erythematosus

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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The Asp 9 Asn Mutation in the Lipoprotein Lipase Gene Is Associated With Increased Progression of Coronary Atherosclerosis

Abstract: This study shows that heterozygosity for a mutation in the LPL gene, which causes only subtle changes in fasting plasma lipids, may promote the progression of coronary atherosclerosis and diminish clinical event-free survival.

Cited by 113 publications

References 17 publications

Haplotypes in the lipoprotein lipase gene influence high-density lipoprotein cholesterol response to statin therapy and progression of atherosclerosis in coronary artery bypass grafts

Haplotypes in the lipoprotein lipase gene influence high-density lipoprotein cholesterol response to statin therapy and progression of atherosclerosis in coronary artery bypass grafts

Autoantibodies to lipoprotein lipase and dyslipidemia in systemic lupus erythematosus

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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The Asp ₉ Asn Mutation in the Lipoprotein Lipase Gene Is Associated With Increased Progression of Coronary Atherosclerosis