<i>ADH</i> Genotype Does Not Modify the Effects of Alcohol on High‐Density Lipoprotein

Whitfield, John B.; OBrien, Martin E.; Nightingale, Brian N.; Zhu, Gu; Heath, Andrew C.; Martin, Nicholas G.

doi:10.1097/01.alc.0000057940.57330.70

Cited by 27 publications

(13 citation statements)

References 20 publications

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“…This has been confirmed in other populations [43], [44]. In addition an interaction between ADH1c and the level of alcohol consumption in relation to HDL has been reported in several studies [42], [45] although not in all [43], [46].…”

Section: Discussionsupporting

confidence: 68%

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The Association of Alcohol and Alcohol Metabolizing Gene Variants with Diabetes and Coronary Heart Disease Risk Factors in a White Population

Husemoen¹,

Jørgensen

Borch‐Johnsen

et al. 2010

PLoS ONE

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BackgroundEpidemiological studies have shown a J- or U-shaped relation between alcohol and type 2 diabetes and coronary heart disease (CHD). The underlying mechanisms are not clear. The aim was to examine the association between alcohol intake and diabetes and intermediate CHD risk factors in relation to selected ADH and ALDH gene variants.Methodology/Principal FindingsCross-sectional study including 6,405 Northern European men and women aged 30–60 years from the general population of Copenhagen, Denmark. Data were collected with self-administered questionnaires, a physical examination, a 2 hour oral glucose tolerance test, and various blood tests. J shaped associations were observed between alcohol and diabetes, metabolic syndrome (MS), systolic and diastolic blood pressure, triglyceride, total cholesterol, and total homocysteine. Positive associations were observed with insulin sensitivity and HDL cholesterol, and a negative association with insulin release. Only a few of the selected ADH and ALDH gene variants was observed to have an effect. The ADH1c (rs1693482) fast metabolizing CC genotype was associated with an increased risk of impaired glucose tolerance (IGT)/diabetes compared to the CT and TT genotypes. Significant interactions were observed between alcohol and ADH1b (rs1229984) with respect to LDL and between alcohol and ALDH2 (rs886205) with respect to IGT/diabetes.Conclusions/SignificanceThe selected ADH and ALDH gene variants had only minor effects, and did not seem to markedly modify the health effects of alcohol drinking. The observed statistical significant associations would not be significant, if corrected for multiple testing.

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Section: Discussionsupporting

confidence: 68%

“…The ADH1b rs1229984 GG slow genotype has been associated with elevated blood pressure, triglycerides, and uric acid in one study of Japanese [47], whereas another study on Europeans found no relation to HDL [46]. We observed a decreased fasting serum LDL level among heavy drinkers with the intermediate/fast ADH1b (rs1229984) GA/AA genotype.…”

Section: Discussionmentioning

confidence: 40%

The Association of Alcohol and Alcohol Metabolizing Gene Variants with Diabetes and Coronary Heart Disease Risk Factors in a White Population

Husemoen¹,

Jørgensen

Borch‐Johnsen

et al. 2010

PLoS ONE

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“…Because this variant ostensibly leads to greater exposure to ethanol upon ingestion (although this has been difficult to measure), it might be anticipated to augment the effects of ethanol. Although data are not entirely consistent [193][194][195][196][197], very suggestive results from the Nurses' Health and Physicians' Health Studies suggest that the effect of alcohol on HDLC may be amplified in a dose-dependent manner among those with slow alleles [198,199]. Surprisingly, the opposite may be true for the relationships of alcohol consumption with diabetes and body weight.…”

Section: Genetic Modification Of the Alcohol-mets Relationshipmentioning

confidence: 98%

Diet and Metabolic Syndrome

Djoussé¹,

Padilla²,

Nelson³

et al. 2010

EMIDDT

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Given the higher burden of risk factors for metabolic syndrome (MetS) on morbidity and mortality, it is critical to prevent the development of metabolic syndrome in the first place. While dietary habits have been favorably associated with some of the factors included in the definition of metabolic syndrome, limited and inconsistent data have been reported on the role of nutrition in the development of metabolic syndrome. Currently, there is no consensus as to which dietary patterns would confer the lowest risk of MetS. Identification of dietary patterns, food groups, or nutrients that may lower the incidence of metabolic syndrome could improve prevention strategies as well as prognosis among subjects with existing MetS. This manuscript reviews current evidence on dietary patterns, consumption of fat, whole grains, carbohydrate quality and quantity, and moderate alcohol consumption as they relate to metabolic syndrome.

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“…Other examples for genes with rare variants having an important influence on HDLC levels are the angiopoietin-like 4 (ANGPTL4) gene (variant E40K, MAF=2%) which was associated with significantly higher levels of HDLC (p=4.0×10 -7 ) in 8726 individuals of the ARIC Study (Romeo et al, 2007) or rare variants in the alcohol dehydrogenase 2 (ADH2) gene (MAF=2.8%) (Whitfield et al, 2003) or in the cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) gene (MAF=0.5%) (Yamada et al, 2007) which showed significant associations in 901 and 3787 individuals, respectively.…”

Section: Common Versus Rare Variantsmentioning

confidence: 99%

Genetic-epidemiological evidence on genes associated with HDL cholesterol levels: A systematic in-depth review

Boes

Coassin

Kollerits

et al. 2009

Experimental Gerontology

117

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High-density lipoprotein (HDL) particles exhibit multiple antiatherogenic effects. They are key players in the reverse cholesterol transport which shuttles cholesterol from peripheral cells (e.g. macrophages) to the liver or other tissues. This complex process is thought to represent the basis for the antiatherogenic properties of HDL particles. The amount of cholesterol transported in HDL particles is measured as HDL cholesterol (HDLC) and is inversely correlated with the risk for coronary artery disease: an increase of 1 mg/dL of HDLC levels is associated with a 2% and 3% decrease of the risk for coronary artery disease in men and women, respectively. Genetically determined conditions with high HDLC levels (e.g. familial hyperalphalipoproteinemia) often coexist with longevity, and higher HDLC levels were found among healthy elderly individuals.HDLC levels are under considerable genetic control with heritability estimates of up to 80%. The identification and characterization of genetic variants associated with HDLC concentrations can provide new insights into the background of longevity. This review provides an extended overview on the current genetic-epidemiological evidence from association studies on genes involved in HDLC metabolism. It provides a path through the jungle of association studies which are sometimes confusing due to the varying and sometimes erroneous names of genetic variants, positions and directions of associations. Furthermore, it reviews the recent findings from genome-wide association studies which have identified new genes influencing HDLC levels.The yet identified genes together explain only a small amount of less than 10% of the HDLC variance, which leaves an enormous room for further yet to be identified genetic variants. This might be accomplished by large population-based genome-wide meta-analyses and by deep-sequencing approaches on the identified genes. The resulting findings will probably result in a re-drawing and extension of the involved metabolic pathways of HDLC metabolism.

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ADH Genotype Does Not Modify the Effects of Alcohol on High‐Density Lipoprotein

Abstract: The concept that alcohol dehydrogenase genotype and alcohol metabolic rate modify the effects of alcohol on plasma HDL concentration is not supported by our results.

Cited by 27 publications

References 20 publications

The Association of Alcohol and Alcohol Metabolizing Gene Variants with Diabetes and Coronary Heart Disease Risk Factors in a White Population

The Association of Alcohol and Alcohol Metabolizing Gene Variants with Diabetes and Coronary Heart Disease Risk Factors in a White Population

Diet and Metabolic Syndrome

Genetic-epidemiological evidence on genes associated with HDL cholesterol levels: A systematic in-depth review

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