Associations of LPL and APOC3 gene polymorphisms on plasma lipids in a Mediterranean population: interaction with tobacco smoking and the APOE locus.
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 epsilon4 than in epsilon3 subjects, and absent in epsilon2 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 epsilon4/H(-) subjects. Understanding this gene-gene-environmental interaction may facilitate preventive interventions to reduce coronary artery disease risk.
Corella
Dolores
D
Genetic and Molecular Epidemiology Unit, Department of Preventive Medicine and Public Health, University of Valencia, Valencia, Spain.
Guillén
Marisa
M
Sáiz
Carmen
C
Portolés
Olga
O
Sabater
Antonio
A
Folch
José
J
Ordovas
Jose M
JM
D000328:Adult; D001056:Apolipoproteins C / Q000235:genetics* / Q000502:physiology; D001057:Apolipoproteins E / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood; D003430:Cross-Sectional Studies; D015247:Deoxyribonuclease HindIII / Q000235:genetics; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D008055:Lipids / Q000097:blood*; D008071:Lipoprotein Lipase / Q000235:genetics* / Q000502:physiology; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics* / Q000502:physiology; D012907:Smoking / Q000235:genetics*; D013030:Spain / Q000453:epidemiology; D014280:Triglycerides / Q000097:blood
D001056:Apolipoproteins C; D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008055:Lipids; D014280:Triglycerides; D008071:Lipoprotein Lipase; D015247:Deoxyribonuclease HindIII; C024408:endodeoxyribonuclease SacI; D015252:Deoxyribonucleases, Type II Site-Specific