title: Variation at the lipoprotein lipase and apolipoprotein AI-CIII gene loci are associated with fasting lipid and lipoprotein traits in a population sample from Iceland: interaction between genotype, gender, and smoking status.
abstract: The effects of polymorphisms in the lipoprotein lipase (LPL) gene (HindIII and S447X) and in the apolipoprotein (apo) AI-CIII gene cluster (G75A and C1100T) on levels of fasting plasma triglycerides, apoCIII, high density lipoprotein cholesterol (HDL-C), and apoAI were examined in 315 healthy men and women from Iceland. Non-smoking and smoking men and women were examined separately because of the strong effects of smoking status and gender on lipoproteins. For the LPL gene, there were no significant associations between plasma traits and genotypes of the S447X polymorphism, but the LPL-HindIII polymorphism was associated with significant effects on levels of all traits, with the effect of genotype on triglycerides and apoAI being modulated by smoking status, (genotype x smoking interaction, P < .02). The H- allele was generally associated with slightly lower levels of apoCIII, with a lowering effect on triglycerides only in smokers and with a raising effect on ApoAI in non-smoking and smoking men and in non-smoking women. For the apoCIII C1100T polymorphism, smoking and non-smoking men with one or more T alleles had levels of triglycerides roughly 10% higher than those with only the C allele; in contrast, the women with the T allele had lower levels of triglycerides (15.7% lower in non-smokers, P = .04; gender x genotype interaction, P = .02). In males and females and in smokers and non-smokers, the T allele was associated with levels of apoCIII that were 9-20% higher than those with only the C allele (P = .004 overall). In the non-smoking men, nonlinear additive effects were observed with combinations of genotypes at the LPL and apoAI-CIII loci, with the HDL-C and apoAI raising effect associated with the A75 allele and H- allele seen only in those men with both alleles, and the apoCIII raising effect associated with the H+ and T alleles seen only in those with both alleles. Thus, variations at both of the LPL and apoAI-apoCIII loci influence levels of triglycerides, apoCIII, HDL-C, and apoAI, but these effects are strongly modulated by smoking and are different between men and women. The mechanisms for these interactions between smoking or gender and genes are unknown, but future studies should take such interactions into account.
authors.affiliation: Department of Medicine, Rayne Institiute, London, United Kingdom.
authors.forename: R E
authors.initials: RE
authors.lastname: Peacock
authors.forename: A
authors.initials: A
authors.lastname: Temple
authors.forename: V
authors.initials: V
authors.lastname: Gudnason
authors.forename: M
authors.initials: M
authors.lastname: Rosseneu
authors.forename: S E
authors.initials: SE
authors.lastname: Humphries
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D016632:Apolipoprotein A-I / Q000097:blood / Q000235:genetics*; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C / Q000097:blood / Q000235:genetics*; D004247:DNA / Q000032:analysis; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007055:Iceland; D008055:Lipids / Q000097:blood*; D008071:Lipoprotein Lipase / Q000097:blood / Q000235:genetics*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D011110:Polymorphism, Genetic; D012737:Sex Factors; D012907:Smoking; D018709:Statistics, Nonparametric
chemical_list: D016632:Apolipoprotein A-I; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C; D008055:Lipids; D008074:Lipoproteins; D004247:DNA; D008071:Lipoprotein Lipase