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Journal of Lipid Research, Vol. 43, 416-427, March 2002
Copyright © 2002 by Lipid Research, Inc.

Associations of LPL and APOC3 gene polymorphisms on plasma lipids in a Mediterranean population: interaction with tobacco smoking and the APOE locus

Correspondence to: Jose M. Ordovas, at the Lipid Metabolism Laboratory, JM-USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington St., Boston, MA 02111., ordovas{at}hnrc.tufts.edu (E-mail)

We conducted a cross-sectional study in a Spanish population (n = 1,029) to investigate associations between the LPL and APOC3 gene loci (LPL-HindIII, LPL-S447X, and APOC3-SstI) and plasma lipid levels and their interaction with APOE polymorphisms and smoking. Carriers of the H^- or the X447 allele had higher levels of HDL cholesterol (HDL-C), and lower levels of TG, after adjustment for age, body mass index, alcohol, smoking, exercise, and education (P < 0.01). The APOC3 polymorphism presented additive effects to the LPL variants on TG and HDL-C levels in men, and on TG in women. The most and the least favorable haplotype combinations were H^-/X447/S1 and H⁺/S447/S2, respectively. These combinations accounted for 7% and 5% of the variation in HDL-C and TG in men, and 3% and 4% in women. There was a significant interaction between APOE and LPL variants and HDL-C levels in both genders (P < 0.05). The increases in HDL-C observed for the rare alleles were higher in 4 than in 3 subjects, and absent in 2 individuals. This effect was modulated by smoking (interaction HindIII-APOE-smoking, P = 0.019), indicating that smoking abolished the increase in HDL-C levels observed in 4/H^- subjects.

Understanding this gene-gene-environmental interaction may facilitate preventive interventions to reduce coronary artery disease risk. — Corella, D., M. Guillén, C. Sáiz, O. Portolés, A. Sabater, J. Folch, and J. M. Ordovas. Associations of LPL and APOC3 gene polymorphisms on plasma lipids in a Mediterranean population: interaction with tobacco smoking and the APOE locus. J. Lipid Res. 2002. 43: 416–427.

Supplementary key words: lipoprotein lipase, apolipoprotein C-III, lipids, gene-environmental interaction

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