%0 Journal Article %J J Stud Alcohol Drugs %D 2007 %T Interaction effects of high-density lipoprotein metabolism gene variation and alcohol consumption on coronary heart disease risk: the atherosclerosis risk in communities study. %A Volcik, Kelly %A Ballantyne, Christie M %A Pownall, Henry J %A Sharrett, A Richey %A Boerwinkle, Eric %K Age Factors %K Alcohol Drinking %K Aryldialkylphosphatase %K Black People %K Cholesterol Ester Transfer Proteins %K Cholesterol, HDL %K Coronary Artery Disease %K Female %K Genetic Predisposition to Disease %K Genetic Variation %K Genotype %K Humans %K Lipase %K Lipoprotein Lipase %K Male %K Middle Aged %K Prospective Studies %K Risk %K Sex Factors %K White People %X

OBJECTIVE: Light to moderate alcohol consumption has been widely established to be protective against coronary heart disease (CHD), whereas heavy alcohol consumption has been shown to have a potential detrimental effect. The reduction in risk of CHD associated with light and moderate alcohol intake is generally attributed to the beneficial effects of alcohol on high-density lipoprotein (HDL) cholesterol levels. Previous research in the Atherosclerosis Risk in Communities (ARIC) study showed all levels of alcohol consumption to be protective against CHD in whites but to be associated with an increased risk of CHD in black men. We investigated the ARIC cohort to determine whether risk of incident CHD is influenced by an interaction effect between alcohol intake and genetic variation involved in the regulation of HDL cholesterol. Genes of interest included cholesterol ester transfer protein (CETP), lipoprotein lipase (LPL), hepatic lipase (HL), and paraoxonase-1 (PON1).

METHOD: Participants were selected from the ARIC study, a prospective investigation of atherosclerosis and its clinical sequelae, involving 15,792 individuals, ages 45-64 years at recruitment (1987-1989). Incident CHD was identified through annual telephone calls and hospital and death certificate surveillance. Because of ethnic differences in the alcohol-CHD relationship observed in the ARIC cohort and pattern of alcohol consumption differences, statistical analyses were evaluated separately for each race-gender stratum (white men/women, black men/women).

RESULTS: Genotype modified the relationship between heavy drinking and CHD risk but did not modify this relationship for light or moderate drinking. Interaction analyses were significant for heavy alcohol intake and PON1 genotype (p=.02) in black men, with a suggested interaction for heavy alcohol intake and CETP genotype (p=.06) in black men. Heavy drinking was associated with an increased risk for CHD in black men with the PON1 QQ and CETP GG genotypes (PON1 hazard rate ratio [HRR]=17.3, 95% confidence interval [CI]: 1.76-170.2; CETP HRR=2.23, 95% CI: 1.01-4.91).

CONCLUSIONS: Results from the current study suggest that interaction effects between alcohol consumption and HDL cholesterol metabolism gene variation influence the risk of incident CHD in black men. Additional studies are warranted to confirm these findings.

%B J Stud Alcohol Drugs %V 68 %P 485-92 %8 2007 Jul %G eng %N 4 %1 https://www.ncbi.nlm.nih.gov/pubmed/17568951?dopt=Abstract %R 10.15288/jsad.2007.68.485 %0 Journal Article %J Arterioscler Thromb Vasc Biol %D 2006 %T Consistent effects of genes involved in reverse cholesterol transport on plasma lipid and apolipoprotein levels in CARDIA participants. %A Klos, Kathy L E %A Sing, Charles F %A Eric Boerwinkle %A Hamon, Sara C %A Rea, Thomas J %A Clark, Andrew %A Fornage, Myriam %A Hixson, James E %K Adult %K Apolipoproteins %K Apolipoproteins A %K Apolipoproteins C %K Apolipoproteins E %K ATP Binding Cassette Transporter 1 %K ATP-Binding Cassette Transporters %K Biological Transport, Active %K Black People %K Carrier Proteins %K Cholesterol %K Cholesterol Ester Transfer Proteins %K Coronary Artery Disease %K Female %K Genetic Predisposition to Disease %K Genotype %K Glycoproteins %K Haplotypes %K Humans %K Lipids %K Male %K Polymorphism, Single Nucleotide %K White People %X

OBJECTIVE: To identify common variations in genes in the reverse cholesterol transport pathway with nongender-specific influence on plasma lipid and apolipoprotein levels.

METHODS AND RESULTS: An average of 5 single nucleotide polymorphisms (SNPs) were genotyped within each of 45 genomic regions (54 genes) in blacks (1131 females and 812 males) and whites (1102 females and 954 males) from the Coronary Artery Risk Development in Young Adults (CARDIA) study. SNPs and gene-based 3-SNP haplotypes were evaluated for their ability to predict variation in plasma apolipoproteins (apo) A-I and apoB, total cholesterol (TC), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides (TG). We identified 14 SNPs in 6 candidate gene regions that explained statistically significant variation in the same trait in both genders of at least one race and with evidence of consistent genotype mean trend across gender within race. Haplotype analyses identified 9 candidate gene regions that explained statistically significant variation in one or both races.

CONCLUSIONS: Four gene regions, ABCA1, APOA1/C3/A4/A5, APOE/C1/C4/C2, and CETP, explained plasma lipoprotein variation most consistently across strata. Other gene regions that influence plasma lipid and apolipoprotein levels within race include CYP7A1, LPL, PPARA, SOAT1, and SREBF2.

%B Arterioscler Thromb Vasc Biol %V 26 %P 1828-36 %8 2006 Aug %G eng %N 8 %1 https://www.ncbi.nlm.nih.gov/pubmed/16763159?dopt=Abstract %R 10.1161/01.ATV.0000231523.19199.45 %0 Journal Article %J Curr Atheroscler Rep %D 2005 %T Pharmacogenetics of response to statins: where do we stand? %A Maitland-van der Zee, Anke-Hilse %A Eric Boerwinkle %K Carrier Proteins %K Cholesterol Ester Transfer Proteins %K Cholesterol, LDL %K Coronary Artery Disease %K Glycoproteins %K Humans %K Hydroxymethylglutaryl-CoA Reductase Inhibitors %K Hypercholesterolemia %K Pharmacogenetics %K Polymorphism, Genetic %X

Cardiovascular disease is one of the leading causes of death, especially in developed countries. Blood cholesterol lowering by way of statin therapy is a common risk-lowering therapy. The risk reduction for coronary artery disease for patients using statins is 27%. These reductions, however, are average effects for all patients included in the trials. There is notable interindividual variation in response to statins, and the origins of this variation are poorly understood. Pharmacogenetics seeks to determine the role of genetic factors in variation of drug response. In patients with primary hypercholesterolemia, 23 studies have examined the effects of genetic polymorphisms at 20 different loci on the lipid response to statin treatment, and 18 studies examined genetic polymorphisms involved in the benefits of statin therapy in the prevention of cardiovascular disease. Even though many studies have been performed, few results have been replicated. It is our contention that larger sample sizes and consideration of multiple genes are needed in the field of pharmacogenetics of statin response.

%B Curr Atheroscler Rep %V 7 %P 204-8 %8 2005 May %G eng %N 3 %1 https://www.ncbi.nlm.nih.gov/pubmed/15811254?dopt=Abstract %R 10.1007/s11883-005-0007-3