Genetic variations at the lipoprotein lipase gene influence plasma lipid concentrations and interact with plasma n-6 polyunsaturated fatty acids to modulate lipid metabolism.

Garcia-Rios A, Delgado-Lista J, Perez-Martinez P, Phillips CM, Ferguson JF, Gjelstad IM, Williams CM, Karlström B, Kieć-Wilk B, Blaak EE, Lairon D, Planells R, Malczewska-Malec M, Defoort C, Riserus U, Saris WH, Lovegrove JA, Drevon CA, Roche HM, Lopez-Miranda J
Atherosclerosis. 2011 218 (2): 416-22

PMID: 21840003 · DOI:10.1016/j.atherosclerosis.2011.07.092

OBJECTIVE - To investigate whether seven common single nucleotide polymorphisms (SNPs) at the lipoprotein lipase (LPL) locus interact with total plasma fatty acids to modulate plasma lipid metabolism in metabolic syndrome (MetS) patients.

METHODS - Plasma fatty acid composition, plasma lipid concentrations and LPL SNPs were determined in 452 subjects with the MetS in the European LIPGENE human study and were repeated in 1754 subjects from the LIPGENE-SU.VI.MAX Study.

RESULTS - Triglycerides (TG) were lower, and HDL higher in the carriers of rs328 and rs1059611 in the SUVIMAX cohort (all P<0.001), and these findings showed a similar, non-significant trend in LIPGENE cohort. In this last cohort, we found a gene-fatty acids interaction, as the carriers of the minor allele displayed a lower fasting TG and triglyceride rich lipoproteins-TG (TRL-TG) concentrations only when they had n-6 polyunsaturated fatty acids below the median (all P<0.05). Moreover, subjects carrying the minor allele for rs328 SNP and with a low level of n-6 PUFA displayed higher nonesterified fatty acid (NEFA) plasma concentrations as compared with homozygous for the major allele (P=0.034). Interestingly, the n-6 PUFA-dependent associations between those SNPs and TG metabolism were also replicated in subjects without MetS from the SU.VI.MAX cohort.

CONCLUSION - Two genetic variations at the LPL gene (rs328 and rs1059611) influence plasma lipid concentrations and interact with plasma n-6 PUFA to modulate lipid metabolism. The knowledge of new genetic factors together with the understanding of these gene-nutrient interactions could help to a better knowledge of the pathogenesis in the MetS.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

MeSH Terms (18)

Adult Aged Alleles Cohort Studies Europe Fatty Acids, Omega-6 Gene Expression Regulation, Enzymologic Genetic Variation Heterozygote Homozygote Humans Lipid Metabolism Lipids Lipoprotein Lipase Metabolic Syndrome Middle Aged Polymorphism, Single Nucleotide Triglycerides

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