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Effect of LSR polymorphism on blood lipid levels and age-specific epistatic interaction with the APOE common polymorphism

Clinical Genetics, doi: 10.1111/cge.13181, volume 93, issue 4, pp. 846-852.

Xie, T., Stathopoulou, M., Akbar, S., Oster, T., Siest, G., Yen Potin, F., Visvikis-Siest, S.

2017

Background The lipolysis stimulated lipoprotein receptor (LSR) is an apolipoprotein (Apo) B and ApoE receptor that participates in the removal of TG-rich lipoproteins during the postprandial phase. LSR gene is located upstream of that for ApoE, an important risk factor for cardiovascular disease (CVD). Since the APOE common polymorphism significantly affects the variability of lipid metabolism, this study aimed to determine the potential impact of a functional SNP in LSR gene on lipid traits in healthy subjects and to investigate potential epistatic interaction between LSR and APOE.

Methods Two populations from the STANISLAS Family Study (SFS) were used: unrelated healthy adults (n = 432) and children (n = 428, <18 years old). The effects of LSR SNP rs916147 on lipid levels and its interaction with ε2 allele of the common polymorphism of APOE gene were investigated.

Results The LSR variant rs916147 was associated with decreased levels of ApoB in both children and adults. Age-specific epistasis was observed between APOE and LSR, reversing the protective effect of APOE ε2 allele on cholesterol, APOE and low-density lipoprotein levels. This interaction was verified in an independent adult population (n=2059).

Conclusions These results highlight the importance of the LSR polymorphism and reveal the existence of complex molecular links between LSR and ApoE for the regulation of lipid levels, revealing potential new pathways of interest in type III hyperlipidemia, and its involvement in CVD pathology.

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