Cigarette smoking and the common B1 allele of the TaqIB polymorphism have both been reported to be associated with increased cholesteryl ester transfer protein (CETP) activity and altered lipoprotein levels. Thus, it is possible that the combined presence of these two respective environmental and genetic factors may enhance cardiovascular risk. We hypothesized that susceptibility to early onset myocardial infarction (MI) among cigarette smokers may be related to the presence of TaqIB polymorphism in the CETP gene.
The age at onset of a first MI among current (n = 199), past (n = 345), and never (n = 270) smokers was related to the presence of the TaqIB1 and B2 alleles in a cohort of 814 first MI patients.
Multivariate regression analysis demonstrated that cigarette smoking was associated with a significant increase in the risk for early onset MI only among carriers of the TaqIB1 allele: current smokers with the B1B1 and B1B2 genotypes displayed a respective 9.4 (P < 0.001) and 8.4 (P < 0.001) year reduction in the age at onset of a first MI compared with never smokers, and past smokers with these genotypes exhibited a respective 3.8 (P = 0.003) and 3.7 (P = 0.01) year reduction. By contrast, current and past smoking was not associated with a significant increase in the risk for early onset MI among B2B2 homozygotes (3.0 [P = 0.28] and 0.2 [P = 0.93] year reduction, respectively). The smoking x genotype interaction was statistically significant (P = 0.04).
The current findings suggest that genetic factors may modify susceptibility to early onset MI among cigarette smokers.
"Genotyping was performed as described previously [12,28,30,31] for: PAI-2 (SERPINB, rs6095), LRP-1 (LRP1, rs1800156), cholesteryl ester transfer protein (CETP, rs708272), p22phox (CYBA, rs4673), and thrombospondin-4 (TSP-4) (THBS4, rs1866389). All were in Hardy-Weinberg equilibrium except for p22phox (CYBA, rs4673). "
[Show abstract][Hide abstract] ABSTRACT: The objective of this work was to investigate whether fibrinolysis plays a role in establishing recurrent coronary event risk in a previously identified group of postinfarction patients. This group of patients was defined as having concurrently high levels of high-density lipoprotein cholesterol (HDL-C) and C-reactive protein (CRP) and was previously demonstrated to be at high-risk for recurrent coronary events. Potential risk associations of a genetic polymorphism of plasminogen activator inhibitor-2 (PAI-2) were probed as well as potential modulatory effects on such risk of a polymorphism of low-density lipoprotein receptor related protein (LRP-1), a scavenger receptor known to be involved in fibrinolysis in the context of cellular internalization of plasminogen activator/plansminogen activator inhibitor complexes. To this end, Cox multivariable modeling was performed as a function of genetic polymorphisms of PAI-2 (SERPINB, rs6095) and LRP-1 (LRP1, rs1800156) as well as a set of clinical parameters, blood biomarkers, and genetic polymorphisms previously demonstrated to be significantly and independently associated with risk in the study population including cholesteryl ester transfer protein (CETP, rs708272), p22phox (CYBA, rs4673), and thrombospondin-4 (THBS4, rs1866389). Risk association was demonstrated for the reference allele of the PAI-2 polymorphism (hazard ratio 0.41 per allele, 95% CI 0.20-0.84, p=0.014) along with continued significant risk associations for the p22phox and thrombospondin-4 polymorphisms. Additionally, further analysis revealed interaction of the LRP-1 and PAI-2 polymorphisms in generating differential risk that was illustrated using Kaplan-Meier survival analysis. We conclude from the study that fibrinolysis likely plays a role in establishing recurrent coronary risk in postinfarction patients with concurrently high levels of HDL-C and CRP as manifested by differential effects on risk by polymorphisms of several genes linked to key actions involved in the fibrinolytic process.
PLoS ONE 07/2013; 8(7):e68920. DOI:10.1371/journal.pone.0068920 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We examine the reasons for investigating gene-environment interactions and address recent reports evaluating interactions between genes and environmental modulators in relation to cardiovascular disease and its common risk factors.
Studies focusing on smoking, physical activity, and alcohol and coffee consumption are observational and include relatively large sample sizes. They tend to examine single genes, however, and fail to address interactions with other genes and other correlated environmental factors. Studies examining gene-diet interactions include both observational and interventional designs. These studies are smaller, especially those including dietary interventions. Among the reported gene-diet interactions, it is important to highlight the strengthened position of APOA5 as a major gene that is involved in triglyceride metabolism and modulated by dietary factors, and the identification of APOA2 as a modulator of food intake and obesity risk.
The study of gene-environment interactions is an active and much needed area of research. Although technical barriers of genetic studies are rapidly being overcome, inclusion of comprehensive and reliable environmental information represents a significant shortcoming of genetics studies. Progress in this area requires inclusion of larger populations but also more comprehensive, standardized, and precise approaches to capturing environmental information.
Current Opinion in Lipidology 05/2008; 19(2):158-67. DOI:10.1097/MOL.0b013e3282f6a809 · 5.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aims of this review were to examine the rationale for investigating the interaction between genes and the environment and to discuss recent studies into the interactions of genes and environmental modulators that are relevant to cardiovascular disease and its principle risk factors.
Studies that have focused on smoking, alcohol and coffee consumption, and physical activity have all been observational studies and have involved relatively large samples. However, they tended to examine single genes and failed to take into account interactions with other genes or associated environmental factors. Both observational and interventional studies have been used to explore the interaction between genes and diet, with interventional studies being much smaller. Of the gene– diet interactions reported, two important highlights are, firstly, the confirmation that the apolipoprotein A-V gene (APOA5) is involved in triglyceride metabolism and is modulated by dietary factors and, secondly, the discovery that apolipoprotein A-II (APOA2) modulates food intake and the risk of obesity.
The study of gene-environment interactions is an active and vital area of research. While the technical barriers to carrying out genetic studies are rapidly being overcome, studies are still hampered by the substantial difficulty of including comprehensive and reliable data on environmental factors. Progress in this area depends on involving large study populations across a range of geographical regions, as well as on employing a more comprehensive, standardized and precise approach to acquiring information about environmental factors.
Revista Española de Cardiología Suplementos 01/2009; 9(2). DOI:10.1016/S1131-3587(09)71503-1
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