The D9N, N291S and S447X Variants in the Lipoprotein Lipase (LPL) Gene Are Not Associated with Type III Hyperlipidemia

Overview

Journal BMC Med Genet

Publisher Biomed Central

Specialty Genetics

Date 2007 Aug 31

PMID 17727701

Citations 3

Authors

David Evans

Frank U Beil

Affiliations

Soon will be listed here.

Abstract

Background: Type III hyperlipidemia (Type III HLP) is associated with homozygosity for the epsilon2 allele of the APOE gene. However only about 10% of epsilon2 homozygotes develop Type III HLP and it is assumed that additional genetic and/or environmental factors are required for its development. Common variants in the LPL gene have been proposed as likely genetic co-factors.

Methods: The frequency of the LPL SNPs D9N, N291S and S447X in 100 patients with hyperlipidemia and APOE2/2 genotype has been determined and compared to that in healthy blood donors and patients with hyperlipidemia.

Results: There were no statistically significant difference in the frequencies of the variants between APOE2/2 patients and controls.

Conclusion: It is unlikely that the D9N, N291S or S447X variants in the LPL gene play an important role in the development of Type III HLP.

Citing Articles

The influence of LPL S447X variants and obesity on lipid profile, oxidative stress, and the risk of T2DM: A case-control study.

Ahmed G, Rahimi Z, Kohsari M, Shakiba E Health Sci Rep. 2023; 6(1):e1031.

PMID: 36605456 PMC: 9808153. DOI: 10.1002/hsr2.1031.

The expression of type III hyperlipoproteinemia: involvement of lipolysis genes.

Henneman P, van der Sman-de Beer F, Moghaddam P, Huijts P, Stalenhoef A, Kastelein J Eur J Hum Genet. 2008; 17(5):620-8.

PMID: 19034316 PMC: 2986263. DOI: 10.1038/ejhg.2008.202.

Unraveling hyperlipidemia type III (dysbetalipoproteinemia), slowly.

Schaefer J Eur J Hum Genet. 2008; 17(5):541-2.

PMID: 19034315 PMC: 2986265. DOI: 10.1038/ejhg.2008.222.

References

Mahley R, Huang Y, Rall Jr S . Pathogenesis of type III hyperlipoproteinemia (dysbetalipoproteinemia). Questions, quandaries, and paradoxes. J Lipid Res. 1999; 40(11):1933-49. View

Sijbrands E, Hoffer M, Meinders A, Havekes L, Frants R, Smelt A . Severe hyperlipidemia in apolipoprotein E2 homozygotes due to a combined effect of hyperinsulinemia and an SstI polymorphism. Arterioscler Thromb Vasc Biol. 1999; 19(11):2722-9. DOI: 10.1161/01.atv.19.11.2722. View

Marks D, Thorogood M, Neil H, Humphries S . A review on the diagnosis, natural history, and treatment of familial hypercholesterolaemia. Atherosclerosis. 2003; 168(1):1-14. DOI: 10.1016/s0021-9150(02)00330-1. View

Evans D, Buchwald A, Beil F . The single nucleotide polymorphism -1131T>C in the apolipoprotein A5 (APOA5) gene is associated with elevated triglycerides in patients with hyperlipidemia. J Mol Med (Berl). 2003; 81(10):645-54. DOI: 10.1007/s00109-003-0465-4. View

Schaap F, Rensen P, Voshol P, Vrins C, van der Vliet H, Chamuleau R . ApoAV reduces plasma triglycerides by inhibiting very low density lipoprotein-triglyceride (VLDL-TG) production and stimulating lipoprotein lipase-mediated VLDL-TG hydrolysis. J Biol Chem. 2004; 279(27):27941-7. DOI: 10.1074/jbc.M403240200. View

Cohen J, Kiss R, Pertsemlidis A, Marcel Y, McPherson R, Hobbs H . Multiple rare alleles contribute to low plasma levels of HDL cholesterol. Science. 2004; 305(5685):869-72. DOI: 10.1126/science.1099870. View

Evans D, Seedorf U, Beil F . Polymorphisms in the apolipoprotein A5 (APOA5) gene and type III hyperlipidemia. Clin Genet. 2005; 68(4):369-72. DOI: 10.1111/j.1399-0004.2005.00510.x. View

Mailly F, Tugrul Y, Reymer P, Bruin T, Seed M, Groenemeyer B . A common variant in the gene for lipoprotein lipase (Asp9-->Asn). Functional implications and prevalence in normal and hyperlipidemic subjects. Arterioscler Thromb Vasc Biol. 1995; 15(4):468-78. DOI: 10.1161/01.atv.15.4.468. View

Busca R, Peinado J, Vilella E, Auwerx J, Deeb S, Vilaro S . The mutant Asn291-->Ser human lipoprotein lipase is associated with reduced catalytic activity and does not influence binding to heparin. FEBS Lett. 1995; 367(3):257-62. DOI: 10.1016/0014-5793(95)00582-t. View

10.

Zhang H, Reymer P, Liu M, Forsythe I, Groenemeyer B, Frohlich J . Patients with apoE3 deficiency (E2/2, E3/2, and E4/2) who manifest with hyperlipidemia have increased frequency of an Asn 291-->Ser mutation in the human LPL gene. Arterioscler Thromb Vasc Biol. 1995; 15(10):1695-703. DOI: 10.1161/01.atv.15.10.1695. View

11.

Brummer D, Evans D, Berg D, Greten H, Beisiegel U, Mann W . Expression of type III hyperlipoproteinemia in patients homozygous for apolipoprotein E-2 is modulated by lipoprotein lipase and postprandial hyperinsulinemia. J Mol Med (Berl). 1998; 76(5):355-64. DOI: 10.1007/s001090050227. View

12.

Wittrup H, Tybjaerg-Hansen A, Nordestgaard B . Lipoprotein lipase mutations, plasma lipids and lipoproteins, and risk of ischemic heart disease. A meta-analysis. Circulation. 1999; 99(22):2901-7. DOI: 10.1161/01.cir.99.22.2901. View

13.

Blom D, ONeill F, Marais A . Screening for dysbetalipoproteinemia by plasma cholesterol and apolipoprotein B concentrations. Clin Chem. 2005; 51(5):904-7. DOI: 10.1373/clinchem.2004.047001. View

14.

Hixson J, Vernier D . Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res. 1990; 31(3):545-8. View