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The D9N, N291S and S447X variants in the lipoprotein lipase (LPL) gene are not associated with Type III hyperlipidemia.

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.

SUBMITTER: Evans D

PROVIDER: S-EPMC2025595 | biostudies-literature | 2007

REPOSITORIES: biostudies-literature

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The D9N, N291S and S447X variants in the lipoprotein lipase (LPL) gene are not associated with Type III hyperlipidemia.

Evans David D Beil Frank U FU

BMC medical genetics 20070829

<h4>Background</h4>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.<h4>Methods</h4>The frequency of the LPL SNPs D9N, N291S and S447X in 100 patients with hyperlipidemia and APOE2/2 ...[more]

PMID: 17727701

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Project description:Lipoprotein Lipase (LPL), a key enzyme in lipid metabolism, catalyzes the hydrolysis of triglycerides (TG) from TG-rich lipoproteins, and serves a bridging function that enhances the cellular uptake of lipoproteins. Abnormalities in LPL function are associated with pathophysiological conditions, including familial combined hyperlipidemia (FCH). Whereas two LPL susceptibility alleles were found to co-segregate in a few FCH kindred, a role for common, protective alleles remains unexplored. The LPL Ser447Stop (S447X) allele is associated with anti-atherogenic lipid profiles and a modest reduction in risk for coronary disease. We hypothesize that significant depletion of the 447X allele exists in combined hyperlipidemia cases versus controls. A case-control design was employed. The polymorphism was assessed by restriction assay in 212 cases and 161 controls. Genotypic, allelic, and phenotypic associations were examined.We found evidence of significant allelic (447Xcontrol: 0.130 vs. 447Xcase: 0.031, chi2 = 29.085; 1df; p < 0.001) and genotypic association (SS: 0.745 vs. 0.939, and SX+XX: 0.255 vs. 0.061) in controls and cases, respectively (chi2 = 26.09; 1df; p < 0.001). In cases, depletion of the 447X allele is associated with a significant elevation in very-low-density lipoprotein cholesterol (VLDL-C, p = 0.045). Consonant with previous studies of this polymorphism, regression models predict that carriers of the 447X allele displayed significantly lower TG, low-density lipoprotein cholesterol (LDL-C) and TG/high-density lipoprotein cholesterol (HDL-C) ratio.These findings suggest a role for the S447X polymorphism in combined hyperlipidemia and demonstrate the importance of evaluating both susceptibility and protective genetic risk factors.

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S447X variant of the lipoprotein lipase gene, lipids, and risk of coronary heart disease in 3 prospective cohort studies.

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| S-EPMC3183417 | biostudies-literature

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| S-EPMC2667509 | biostudies-literature

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