The lipoprotein lipase gene in combined hyperlipidemia: evidence of a protective allele depletion

Wung, Shu Fen; Kulkarni, Medha V.; Pullinger, Clive R.; Malloy, Mary J.; Kane, John P.; Aouizerat, Bradley E.

doi:10.1186/1476-511x-5-19

Cited by 19 publications

(7 citation statements)

References 57 publications

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“…In several studies, S447X polymorphism has played a protective role in CAD although in a recent study the result is different. 1 , 12 , 14 , 16 Perhaps, S447X polymorphism has affected another function in our population that increases the risk for disease and did not have any protection effect.…”

Section: Discussionmentioning

confidence: 65%

“…We could observe that as previous studies, in this study, there were associations between demographic risk factors (smoking, hypertension, hyperlipidemia, TG> 200 mg/dl and HDL<40 mg/dl) and CAD. 2 , 9 , 12 , 14 , 15 These risk factors were due to the increase in the susceptibility to CAD. Smoking had the most influence on this disease ( smoking: P <0.001, OR=3.256, 95% CI=1.781-5.953; hypertension: P =0.025, OR=1.952, 95% CI=1.086-3.508; hyperlipidemia: P =0.004, OR=2.347, 95% CI=1.315-4.189; TG>200 mg/dl: P =0.004, OR=2.345, 95% CI=1.321-4.161; HDL<40 mg/dl: P =0.024, OR=1.917, 95% CI=1.090-3.372).…”

Section: Discussionmentioning

confidence: 99%

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The Association of Lipoprotein Lipase Genes, HindIII and S447X Polymorphisms With Coronary Artery Disease in Shiraz City

Ahmadi¹,

Senemar²,

Toosi³

et al. 2015

J Cardiovasc Thorac Res

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Introduction: Several polymorphisms at the lipoprotein lipase (LPL) locus are associated with variations in LPL activity serum lipid concentrations and the risk of coronary artery disease (CAD). The aim of this study was to investigate the role of the LPL S447X and HindIII polymorphism in a sample of subjects with CAD and compare them with healthy subjects. Methods: The study enrolled 115 patients and 89 healthy subjects who were recruited from Namazi hospital in 2010-2012. The presence of two common polymorphisms of the LPL gene (HindIII and S447X) was determined by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis using genomic DNA. SPSS 16.0 was used for statistical analysis. Results: S447X was significantly different between the patients with CAD and the healthy subjects (P < 0.001). But HindIII was not significantly different between the patients with CAD and the healthy subjects (P = 0.741). Risk factors such as smoking, hypertension, hyperlipidemia, triglyceride (TG) and high-density lipoprotein (HDL) levels had a significant association with CAD. Conclusion: In our study, the presence of G allele S447X polymorphism increases the TG level and decrease HDL level, so it increases the susceptibility CAD. Moreover, HindIII polymorphism did not have any significant association with CAD.

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Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

The Association of Lipoprotein Lipase Genes, HindIII and S447X Polymorphisms With Coronary Artery Disease in Shiraz City

Ahmadi¹,

Senemar²,

Toosi³

et al. 2015

J Cardiovasc Thorac Res

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“…Many studies have focused on the relationship between LPL gene polymorphism and the incidence of cardiovascular disease in various populations [ 14 , 16 , 19 , 21 , 22 ]. Some studies investigated the influence of LPL gene activity on levels of plasma TG, TC, HDL-c and apolipoproteins, but the results are inconsistent [ 17 , 22 – 26 ]. Clee et al (2000) [ 23 ] demonstrated that decreased plasma LPL activity is associated with high TGs and low HDL phenotypes in patient samples and Ser447Ter mutation is associated with higher plasma LPL activity.…”

Section: Resultsmentioning

confidence: 99%

DNA Polymorphisms of the Lipoprotein Lipase Gene and Their Association with Coronary Artery Disease in the Saudi Population

Al‐Jafari

Daoud

Mobeirek

et al. 2012

IJMS

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Coronary heart disease (CHD) is a major health problem and a major cause of death in most countries. Evidence has been presented that gene polymorphisms (HindIII, PvuII and Ser447Ter) of lipoprotein lipase (LPL) are risk factors of coronary artery disease (CAD).AimOur objective of the present investigation was to determine whether 3 LPL polymorphisms (LPL-HindIII, LPL-PvuII and LPL-Ser447Ter) can be considered as independent risk factors for CAD in the Saudi population.MethodsWe recruited 120 CAD subjects, confirmed angiographically with identical ethnic backgrounds and 65 control subjects. Polymerase chain reaction-restriction fragment length polymorphisms (RFLP) technique was used to detect the polymorphisms of the LPL gene.Results and conclusionFor the HindIII genotype, within the CAD group, the frequencies of the H+H+ were found in 50.8%, whereas 44.2% carried the H−H+ genotype, and 5% carried the H−H− genotype. Within the control group, the H+H+ genotype was found in 44.6%, whereas 35.4% carried the H−H+ genotype, 20% carried the H−H− genotype. The odds ratio (OR) of HindIII genotype H+H+ vs. H−H− genotype at 95% Confidence Interval (CI) were 4.6 (1.57–13.2) and p < 0.005, hence showing no significant association with CAD. For the PvuII genotype, within the CAD group the frequencies of the P+P+ found in 41.7% whereas 43.3.2% carried the P−P+ genotype, and 15% carried the P−P− genotype. Within the control group the P+P+ was found in 38.5%, 43.0% carried the P−P+ genotype, and 18.5% carried the P−P− genotype. The OR of PvuII genotype P+P+ vs. P−P− genotypes (95% CI) is 1.33 and p = 0.52; hence, it was also insignificant to show association with the disease. For the Ser447Ter genotype, within the CAD group, the frequencies of the C/C found in 83.3%, whereas 16.7% carried the C/G genotype. Within the control group, the C/C was found in 87.7% and 12.3% carried the C/G genotype. We did not get any GG genotypes in control as well as patients for this gene. It can be concluded that C allele of gene masks the presence of G allele in the Saudi population. The OR of CG + GG vs. CC (95% CI) is 1.43 from 0.59 to 3.44 which is insignificant. Hence this gene also has no significant association with CAD in the Saudi population.

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“…Interestingly, we noted that ANGPTL3/8 was directly correlated with LDL-C, while ANGPTL4/8 was not. This could be related to LPL-facilitated uptake of cholesterol-containing lipoprotein particles into the liver via VLDL and related receptors ( 87 , 98 – 102 ). Our data demonstrating that ANGPTL3/8 inhibited LPL-facilitated hepatocyte VLDL-C uptake might provide a possible explanation for the positive correlation of ANGPTL3/8 with LDL-C, but further mechanistic investigations along these lines will be needed.…”

Section: Discussionmentioning

confidence: 99%

Angiopoietin-like protein 8 differentially regulates ANGPTL3 and ANGPTL4 during postprandial partitioning of fatty acids

Chen

Pottanat

Siegel

et al. 2020

Journal of Lipid Research

107

223

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Angiopoietin-like protein 8 (ANGPTL8) has been implicated in metabolic syndrome and reported to regulate adipose FA uptake through unknown mechanisms. Here, we studied how complex formation of ANGPTL8 with ANGPTL3 or ANGPTL4 varies with feeding to regulate lipoprotein lipase (LPL). In human serum, ANGPTL3/8 and ANGPTL4/8 complexes both increased postprandially, correlated negatively with HDL, and correlated positively with all other metabolic syndrome markers. ANGPTL3/8 also correlated positively with LDL-cholesterol and blocked LPL-facilitated hepatocyte VLDL-cholesterol uptake. LPL-inhibitory activity of ANGPTL3/8 was >100-fold more potent than that of ANGPTL3, and LPL-inhibitory activity of ANGPTL4/8 was >100-fold less potent than that of ANGPTL4. Quantitative analyses of inhibitory activities and competition experiments among the complexes suggested a model in which localized ANGPTL4/8 blocks the LPL-inhibitory activity of both circulating ANGPTL3/8 and localized ANGPTL4, allowing lipid sequestration into fat rather than muscle during the fed state. Supporting this model, insulin increased ANGPTL3/8 secretion from hepatocytes and ANGPTL4/8 secretion from adipocytes. These results suggest that low ANGPTL8 levels during fasting enable ANGPTL4-mediated LPL inhibition in fat tissue to minimize adipose FA uptake. During feeding, increased ANGPTL8 increases ANGPTL3 inhibition of LPL in muscle via circulating ANGPTL3/8, while decreasing ANGPTL4 inhibition of LPL in adipose tissue through localized ANGPTL4/8, thereby increasing FA uptake into adipose tissue. Excessive caloric intake may shift this system toward the latter conditions, possibly predisposing to metabolic syndrome.

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The lipoprotein lipase gene in combined hyperlipidemia: evidence of a protective allele depletion

Cited by 19 publications

References 57 publications

The Association of Lipoprotein Lipase Genes, HindIII and S447X Polymorphisms With Coronary Artery Disease in Shiraz City

The Association of Lipoprotein Lipase Genes, HindIII and S447X Polymorphisms With Coronary Artery Disease in Shiraz City

DNA Polymorphisms of the Lipoprotein Lipase Gene and Their Association with Coronary Artery Disease in the Saudi Population

Angiopoietin-like protein 8 differentially regulates ANGPTL3 and ANGPTL4 during postprandial partitioning of fatty acids

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