Alcohol Intake and Blood Pressure: A Systematic Review Implementing a Mendelian Randomization Approach
Background:
Alcohol has been reported to be a common and modifiable risk factor for hypertension. However, observational studies are subject to confounding by other behavioural and sociodemographic factors, while clinical trials are difficult to implement and have limited follow-up time. Mendelian randomization can provide robust evidence on the nature of this association by use of a common polymorphism in aldehyde dehydrogenase 2 (ALDH2) as a surrogate for measuring alcohol consumption. ALDH2 encodes a major enzyme involved in alcohol metabolism. Individuals homozygous for the null variant (*2*2) experience adverse symptoms when drinking alcohol and consequently drink considerably less alcohol than wild-type homozygotes (*1*1) or heterozygotes. We hypothesise that this polymorphism may influence the risk of hypertension by affecting alcohol drinking behaviour.
Methods and Findings:
We carried out fixed effect meta-analyses of the ALDH2 genotype with blood pressure (five studies, n = 7,658) and hypertension (three studies, n = 4,219) using studies identified via systematic review. In males, we obtained an overall odds ratio of 2.42 (95% confidence interval [CI] 1.66–3.55, p = 4.8 × 10−6) for hypertension comparing *1*1 with *2*2 homozygotes and an odds ratio of 1.72 (95% CI 1.17–2.52, p = 0.006) comparing heterozygotes (surrogate for moderate drinkers) with *2*2 homozygotes. Systolic blood pressure was 7.44 mmHg (95% CI 5.39–9.49, p = 1.1 × 10−12) greater among *1*1 than among *2*2 homozygotes, and 4.24 mmHg (95% CI 2.18–6.31, p = 0.00005) greater among heterozygotes than among *2*2 homozygotes.
Conclusions:
These findings support the hypothesis that alcohol intake has a marked effect on blood pressure and the risk of hypertension.
Vyšlo v časopise:
Alcohol Intake and Blood Pressure: A Systematic Review Implementing a Mendelian Randomization Approach. PLoS Med 5(3): e52. doi:10.1371/journal.pmed.0050052
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pmed.0050052
Souhrn
Background:
Alcohol has been reported to be a common and modifiable risk factor for hypertension. However, observational studies are subject to confounding by other behavioural and sociodemographic factors, while clinical trials are difficult to implement and have limited follow-up time. Mendelian randomization can provide robust evidence on the nature of this association by use of a common polymorphism in aldehyde dehydrogenase 2 (ALDH2) as a surrogate for measuring alcohol consumption. ALDH2 encodes a major enzyme involved in alcohol metabolism. Individuals homozygous for the null variant (*2*2) experience adverse symptoms when drinking alcohol and consequently drink considerably less alcohol than wild-type homozygotes (*1*1) or heterozygotes. We hypothesise that this polymorphism may influence the risk of hypertension by affecting alcohol drinking behaviour.
Methods and Findings:
We carried out fixed effect meta-analyses of the ALDH2 genotype with blood pressure (five studies, n = 7,658) and hypertension (three studies, n = 4,219) using studies identified via systematic review. In males, we obtained an overall odds ratio of 2.42 (95% confidence interval [CI] 1.66–3.55, p = 4.8 × 10−6) for hypertension comparing *1*1 with *2*2 homozygotes and an odds ratio of 1.72 (95% CI 1.17–2.52, p = 0.006) comparing heterozygotes (surrogate for moderate drinkers) with *2*2 homozygotes. Systolic blood pressure was 7.44 mmHg (95% CI 5.39–9.49, p = 1.1 × 10−12) greater among *1*1 than among *2*2 homozygotes, and 4.24 mmHg (95% CI 2.18–6.31, p = 0.00005) greater among heterozygotes than among *2*2 homozygotes.
Conclusions:
These findings support the hypothesis that alcohol intake has a marked effect on blood pressure and the risk of hypertension.
Zdroje
1. MarmotMGElliottPShipleyMJDyerARUeshimaHU
1994
Alcohol and blood pressure: the INTERSALT study.
BMJ
308
1263
1267
2. PatelRLawlorDAWhincupPMontanerDPapacostaO
2006
The detection, treatment and control of high blood pressure in older British adults: cross-sectional findings from the British Women's Heart and Health Study and the British Regional Heart Study.
J Hum Hypertens
20
733
741
3. FuchsFDChamblessLEWheltonPKNietoFJHeissG
2001
Alcohol consumption and the incidence of hypertension : The Atherosclerosis Risk in Communities Study.
Hypertension
37
1242
1250
4. MooreRDLevineDMSouthardJEntwisleGShapiroS
1990
Alcohol consumption and blood pressure in the 1982 Maryland Hypertension Survey.
Am J Hypertens
3
1
7
5. Davey SmithGEbrahimS
2003
‘Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease.
Int J Epidemiol
32
1
22
6. BosronWFLiTK
1986
Genetic polymorphism of human liver alcohol and aldehyde dehydrogenases, and their relationship to alcohol metabolism and alcoholism.
Hepatology
6
502
510
7. YoshidaAHuangIYIkawaM
1984
Molecular abnormality of an inactive aldehyde dehydrogenase variant commonly found in Orientals.
Proc Natl Acad Sci U S A
81
258
261
8. EnomotoNTakaseSYasuharaMTakadaA
1991
Acetaldehyde metabolism in different aldehyde dehydrogenase-2 genotypes.
Alcohol Clin Exp Res
15
141
144
9. LewisSJDavey SmithG
2005
Alcohol, ALDH2, and esophageal cancer: a meta-analysis which illustrates the potentials and limitations of a Mendelian randomization approach.
Cancer Epidemiol Biomarkers Prev
14
1967
1971
10. PittlerMHWhiteARStevinsonCErnstE
2003
Effectiveness of artichoke extract in preventing alcohol-induced hangovers: a randomized controlled trial.
CMAJ
169
1269
1273
11. NishimuraFTFukunagaTKajiuraHUmenoKTakakuraH
2002
Effects of aldehyde dehydrogenase-2 genotype on cardiovascular and endocrine responses to alcohol in young Japanese subjects.
Auton Neurosci
102
60
70
12. MackenzieISMaki-PetajaKMMcEnieryCMBaoYPWallaceSM
2005
Aldehyde dehydrogenase 2 plays a role in the bioactivation of nitroglycerin in humans.
Arterioscler Thromb Vasc Biol
25
1891
1895
13. HashimotoYNakayamaTFutamuraAOmuraMNakaraiH
2002
Relationship between genetic polymorphisms of alcohol-metabolizing enzymes and changes in risk factors for coronary heart disease associated with alcohol consumption.
Clin Chem
48
1043
1048
14. OkayamaAUeshimaHYamakawaMKitaY
1994
Low-Km aldehyde dehydrogenase-deficiency does not influence the elevation of blood-pressure by alcohol.
J Hum Hypertens
8
205
208
15. EggerMDavey SmithGSchneiderMMinderC
1997
Bias in meta-analysis detected by a simple, graphical test.
BMJ
315
629
634
16. BeggCBMazumdarM
1994
Operating characteristics of a rank correlation test for publication bias.
Biometrics
50
1088
1101
17. MurrayMP
2006
Econometrics: A modern introduction
Boston
Addison-Wesley
18. AmamotoKOkamuraTTamakiSKitaYTsujitaY
2002
Epidemiologic study of the association of low-K-m mitochondrial acetaldehyde dehydrogenase genotypes with blood pressure level and the prevalence of hypertension in a general population.
Hypertens Res
25
857
864
19. TakagiSBabaSIwaiNFukudaMKatsuyaT
2001
The aldehyde dehydrogenase 2 gene is a risk factor for hypertension in Japanese but does not alter the sensitivity to pressor effects of alcohol: The Suita Study.
Hypertens Res
24
365
370
20. TsuritaniIIkaiEDateTSuzukiYIshizakiN
1995
Polymorphism in Aldh2-Genotype in Japanese men and the alcohol-blood pressure relationship.
Am J Hypertens
8
1053
1059
21. HowesLGReidJL
1986
Changes in blood pressure and autonomic reflexes following regular, moderate alcohol consumption.
J Hypertens
4
421
425
22. RositoGAFuchsFDDuncanBB
1999
Dose-dependent biphasic effect of ethanol on 24-h blood pressure in normotensive subjects.
Am J Hypertens
12
236
240
23. BeulensJWJRimmEBAscherioASpiegelmanDHendriksHFJ
2007
Alcohol consumption and risk for coronary heart disease among men with hypertension.
Ann Intern Med
146
10
19
24. Westerterp-PlantengaMSVerwegenCR
1999
The appetizing effect of an aperitif in overweight and normal-weight humans.
Am J Clin Nutr
69
205
212
25. LukasiewiczEMennenLIBertraisSArnaultNPreziosiP
2005
Alcohol intake in relation to body mass index and waist-to-hip ratio: the importance of type of alcoholic beverage.
Public Health Nutr
8
315
320
26. SakuraiMMiuraKTakamuraTOtaTIshizakiM
2006
Gender differences in the association between anthropometric indices of obesity and blood pressure in Japanese.
Hypertens Res
29
75
80
27. ErikssonCJ
2001
The role of acetaldehyde in the actions of alcohol (update 2000).
Alcohol Clin Exp Res
25
15S
32S
28. SaitoKYokoyamaJYoshiikeNDateCYamamotoA
2003
Do the ethanol metabolizing enzymes modify the relationship between alcohol consumption and blood pressure.
J Hypertens
21
1097
1105
29. YamadaYImaiTIshizakiMHondaR
2006
ALDH2 and CYP2E1 genotypes, urinary acetaldehyde excretion and the health consequences in moderate alcohol consumers.
J Hum Genet
51
104
111
30. Davey SmithGEbrahimS
2005
Folate supplementation and cardiovascular disease.
Lancet
366
1679
1681
31. IwaiNTagoNYasuiNKokuboYInamotoN
2004
Genetic analysis of 22 candidate genes for hypertension in the Japanese population.
J Hypertens
22
1119
1126
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