Alcohol dehydrogenase type 1C (ADH1C) variants, alcohol consumption traits, HDL-cholesterol and risk of coronary heart disease in women and men: British Women's Heart and Health Study and Caerphilly cohorts

Ebrahim, Shah; Lawlor, Debbie A.; Ben-Shlomo, Yoav; Timpson, Nicholas J.; Harbord, Roger; Christensen, Mikkel; Baban, Jamil; Kiessling, Matt; Day, Ian N.M.; Gaunt, Tom R.; Smith, George Davey

doi:10.1016/j.atherosclerosis.2007.02.002

Cited by 30 publications

(30 citation statements)

References 27 publications

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“…28,29 However, this finding has not been observed in all studies. 30 We observed that 3 SNPs in 2 lipid metabolism genes were associated with the levels of Apo B/A1 ratio and with acute MI. The association of the Apo E isoforms with MI became Figure 3.…”

Section: Discussionmentioning

confidence: 83%

Genetic Variants Associated With Myocardial Infarction Risk Factors in Over 8000 Individuals From Five Ethnic Groups

Anand

Xie

Paré

et al. 2009

Circ Cardiovasc Genet

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Background-Myocardial infarction (MI) is a leading cause of death globally, but specific genetic variants that influence MI and MI risk factors have not been assessed on a global basis. Methods and Results-We included 8795 individuals of European, South Asian, Arab, Iranian, and Nepalese origin from the INTERHEART case-control study that genotyped 1536 single-nucleotide polymorphisms (SNPs) from 103 genes. One hundred and two SNPs were nominally associated with MI, but the statistical significance did not remain after adjustment for multiple testing. A subset of 940 SNPs from 69 genes were tested against MI risk factors. One hundred and sixty-three SNPs were nominally associated with a MI risk factor and 13 remained significant after adjusting for multiple testing. Of these 13, 11 were associated with apolipoprotein (Apo) B/A1 levels: 8 SNPs from 3 genes were associated with Apo B, and 3 cholesteryl ester transfer protein SNPs were associated with Apo A1. Seven of 8 of the SNPs associated with Apo B levels were nominally associated with MI (PϽ0.05), whereas none of the 3 cholesteryl ester transfer protein SNPs were associated with MI (PՆ0.17). Of the 3 SNPs most significantly associated with MI, rs7412, which defines the Apo E2 isoform, was associated with both a lower Apo B/A1 ratio (Pϭ1.0ϫ10

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Section: Discussionmentioning

confidence: 83%

Genetic Variants Associated With Myocardial Infarction Risk Factors in Over 8000 Individuals From Five Ethnic Groups

Anand

Xie

Paré

et al. 2009

Circ Cardiovasc Genet

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“…Thus, eight studies met our inclusion criteria of which one was examining stroke [13]. Eligible studies on ischemic heart disease included studies on CHD [7], [8], [12], MI [9], [10], and acute coronary events [11]. In total, two of the identified studies analyzed SNP rs1229984 in the ADH1B gene [10], [11] and seven analyzed either SNP rs698 [8], [9], [10], [12], [13] or rs1693482 [7], [11] in the ADH1C gene.…”

Section: Methodsmentioning

confidence: 99%

“…In line with the hypothesis that ethanol is largely responsible for the inverse association between alcohol consumption and coronary events, individuals with the slow ADH1C*2/2 genotype had a lower risk of myocardial infarction (MI) in a study among male physicians [9]. However, later studies on this subject were inconsistent [7], [8], [10], [11], [12]. Comparable data on polymorphisms in ADH1B is rare because of the low frequency of the ADH1B * 2 allele in caucasians [14].…”

Section: Introductionmentioning

confidence: 99%

“…A few prospective studies have investigated the association between alcohol consumption and risk of cardiovascular diseases (CVD) in combination with variations in genes coding for ADH1C or ADH1B [7], [8], [9], [10], [11], [12], [13]. In line with the hypothesis that ethanol is largely responsible for the inverse association between alcohol consumption and coronary events, individuals with the slow ADH1C*2/2 genotype had a lower risk of myocardial infarction (MI) in a study among male physicians [9].…”

Section: Introductionmentioning

confidence: 99%

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Alcohol Consumption, Genetic Variants in Alcohol Deydrogenases, and Risk of Cardiovascular Diseases: A Prospective Study and Meta-Analysis

et al. 2012

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ObjectiveFirst, to investigate and compare associations between alcohol consumption and variants in alcohol dehydrogenase (ADH) genes with incidence of cardiovascular diseases (CVD) in a large German cohort. Second, to quantitatively summarize available evidence of prospective studies on polymorphisms in ADH1B and ADH1C and CVD-risk.MethodsWe conducted a case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort including a randomly drawn subcohort (n = 2175) and incident cases of myocardial infarction (MI; n = 230) or stroke (n = 208). Mean follow-up time was 8.2±2.2 years. The association between alcohol consumption, ADH1B or ADH1C genotypes, and CVD-risk was assessed using Cox proportional hazards regression. Additionally, we report results on associations of variants in ADH1B and ADH1C with ischemic heart disease and stroke in the context of a meta-analysis of previously published prospective studies published up to November 2011.ResultsCompared to individuals who drank >0 to 6 g alcohol/d, we observed a reduced risk of MI among females consuming >12 g alcohol/d (HR = 0.31; 95% CI: 0.10–0.97) and among males consuming >24 to 60 g/d (HR = 0.57; 95% CI: 0.33–0.98) or >60 g alcohol/d (HR = 0.30; 95% CI: 0.12–0.78). Stroke risk was not significantly related to alcohol consumption >6 g/d, but we observed an increased risk of stroke in men reporting no alcohol consumption. Individuals with the slow-coding ADH1B*1/1 genotype reported higher median alcohol consumption. Yet, polymorphisms in ADH1B or ADH1C were not significantly associated with risk of CVD in our data and after pooling results of eligible prospective studies [ADH1B*1/1: RR = 1.35 (95% CI: 0.98–1.88; p for heterogeneity: 0.364); ADH1C*2/2: RR = 1.07 (95% CI: 0.90–1.27; p for heterogeneity: 0.098)].ConclusionThe well described association between alcohol consumption and CVD-risk is not reflected by ADH polymorphisms, which modify the rate of ethanol oxidation.

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“…For the discovery stage, we studied individuals from three population-based cohorts: The British Women’s Heart and Health Study (BWHHS, n= 3443) 12 , the Genetic Regulation of Arterial Pressure of Humans in the Community (GRAPHIC) Study (n= 2024) 13 and the Whitehall II Study (WHII) (n=5059). 14 The replication cohorts comprised individuals from the British Regional Heart Study (n=3519) 15 , the British Genetics of Hypertension (BRIGHT) Study (n=1198) 16 and the Prevention of Renal and Vascular End stage Disease (PREVEND) Study (n=7060) 17 .…”

Section: Methodsmentioning

confidence: 99%

Four Genetic Loci Influencing Electrocardiographic Indices of Left Ventricular Hypertrophy

Shah

Nelson

Gaunt

et al. 2011

Circ Cardiovasc Genet

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Background Presence of left ventricular hypertrophy on an electrocardiogram (ECG-LVH) is widely assessed clinically and provides prognostic information in some settings. There is evidence for significant heritability of ECG-LVH. We conducted a large-scale gene-centric association analysis of four commonly measured indices of ECG-LVH. Methods and Results We calculated Sokolow-Lyon Index, Cornell Product, 12-lead QRS Voltage Sum and 12-lead QRS Voltage Product in 10,256 individuals from 3 population based cohorts and typed their DNA using a customised gene array (the Illumina HumanCVD BeadChip 50K array) containing 49,094 genetic variants in ~2100 genes of cardiovascular relevance. We followed up promising associations in 11,777 additional individuals. We identified and replicated four loci associated with ECG-LVH indices - 3p22.2 (SCN5A, rs6797133, p=1.22×10−7) with Cornell Product and 12q13.3 (PTGES3, rs2290893, p=3.74×10−8), 15q25.2 (NMB, rs2292462, p=3.23×10−9) and 15q26.3 (IGF1R, rs4966014, p=1.26×10−7) with 12-lead QRS Voltage Sum. The odds ratio of being in the top decile for 12-lead QRS Voltage Sum for those carrying 6 trait-raising alleles at the 12q13.3, 15q25.2 and 15q26.3 loci versus those carrying 0–1 alleles was 1.60 (95% CI: 1.20 – 2.29). Lead SNPs at the 12q13.3 and 15q25.2 loci showed significant eQTL effects in monocytes. Conclusions These findings provide novel insights into the genetic determination of ECG-LVH. The findings could help to improve our understanding of the mechanisms determining this prognostically important trait.

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Alcohol dehydrogenase type 1C (ADH1C) variants, alcohol consumption traits, HDL-cholesterol and risk of coronary heart disease in women and men: British Women's Heart and Health Study and Caerphilly cohorts

Cited by 30 publications

References 27 publications

Genetic Variants Associated With Myocardial Infarction Risk Factors in Over 8000 Individuals From Five Ethnic Groups

Genetic Variants Associated With Myocardial Infarction Risk Factors in Over 8000 Individuals From Five Ethnic Groups

Alcohol Consumption, Genetic Variants in Alcohol Deydrogenases, and Risk of Cardiovascular Diseases: A Prospective Study and Meta-Analysis

Four Genetic Loci Influencing Electrocardiographic Indices of Left Ventricular Hypertrophy

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