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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
Dolores Corellaa,
Marisa Guilléna,
Carmen Sáiza,
Olga Portolésa,
Antonio Sabatera,
José Folcha, and
Jose M. Ordovasa,b
a Genetic and Molecular Epidemiology Unit, Department of Preventive Medicine and Public Health, University of Valencia, Valencia, Spain
b JM-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA
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: 416427.
Supplementary key words:
lipoprotein lipase, apolipoprotein C-III, lipids, gene-environmental interaction

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Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
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