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Association of a functional single-nucleotide polymorphism in the ALDH2 gene with essential hypertension depends on drinking behavior in a Chinese Han population

Journal of Human Hypertension volume 27, pages 181–186 (2013)Cite this article

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Abstract

Alcohol consumption is an important environmental factor in the development of essential hypertension (EH) and cardiovascular disease. Several epidemiological studies have investigated the association between hypertension and acetaldehyde dehydrogenase 2 (ALDH2) genotype, although the results are inconsistent. The aim of the present study was to evaluate the possible effect of drinking behavior on the ALDH2–EH relationship in a Chinese Han population. A total of 1098 unrelated individuals with EH and 1021 controls of Chinese Han ethnicity were included. We evaluated the effect of three tag single-nucleotide polymorphisms on blood pressure (BP) and serum lipid level by blood chemical assays. The major findings were that rs671 guanine/adenine genotype (odds ratio (OR)=0.45, 95% confidence interval (CI): 0.28–0.74) and A allele (OR=0.55, 95% CI: 0.36–0.85) were associated with a decreased risk of EH in drinkers. In addition, the rs671 genotype influenced BP, triglyceride (TG) level and high-density lipoprotein cholesterol (HDL-C) level in the same drinking-dependent pattern. Drinkers who carried the A allele displayed lower systolic BP (β=−0.16, P=0.001) and TG level (β=−0.14, P=0.004) and higher HDL-C level (β=0.11, P=0.019), but this association was not observed in nondrinkers. In summary, we present evidence for the association of rs671 in the ALDH2 gene with susceptibility to EH, increase in BP and disturbance of serum lipid profiles in drinkers, but not in nondrinkers. Further functional research is warranted to elucidate the role of rs671 in the variation of BP and lipid levels in EH.

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References

  1. Gu D, Reynolds K, Wu X, Chen J, Duan X, Muntner P et al. Prevalence, awareness, treatment, and control of hypertension in China. Hypertension 2002; 40 (6): 920–927.

    Article  CAS  PubMed  Google Scholar 

  2. He J, Gu D, Chen J, Wu X, Kelly TN, Huang JF et al. Premature deaths attributable to blood pressure in China: a prospective cohort study. Lancet 2009; 374 (9703): 1765–1772.

    Article  Google Scholar 

  3. Taal HR, Verwoert GC, Demirkan A, Janssens AC, Rice K, Ehret G et al. Genome-wide profiling of blood pressure in adults and children. Hypertension 2012; 59 (2): 241–247.

    Article  CAS  Google Scholar 

  4. Ehret GB, Munroe PB, Rice KM, Bochud M, Johnson AD, Chasman DI et al. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature 2011; 478 (7367): 103–109.

    Article  CAS  PubMed  Google Scholar 

  5. Franks PW . Identifying genes for primary hypertension: methodological limitations and gene-environment interactions. J Hum Hypertens 2009; 23 (4): 227–237.

    Article  CAS  Google Scholar 

  6. Fuchs FD, Chambless LE, Whelton PK, Nieto FJ, Heiss G . Alcohol consumption and the incidence of hypertension: The Atherosclerosis Risk in Communities Study. Hypertension 2001; 37 (5): 1242–1250.

    Article  CAS  Google Scholar 

  7. Chen L, Davey Smith G, Harbord RM, Lewis SJ . Alcohol intake and blood pressure: a systematic review implementing a Mendelian randomization approach. PLoS Med 2008; 5 (3): e52.

    Article  PubMed  Google Scholar 

  8. Singh S, Fritze G, Fang BL, Harada S, Paik YK, Eckey R et al. Inheritance of mitochondrial aldehyde dehydrogenase: genotyping in Chinese, Japanese and South Korean families reveals dominance of the mutant allele. Hum Genet 1989; 83 (2): 119–121.

    Article  CAS  Google Scholar 

  9. Takeshita T, Morimoto K, Mao XQ, Hashimoto T, Furuyama J . Phenotypic differences in low Km aldehyde dehydrogenase in Japanese workers. Lancet 1993; 341 (8848): 837–838.

    Article  CAS  Google Scholar 

  10. Harada S, Agarwal DP, Goedde HW, Tagaki S, Ishikawa B . Possible protective role against alcoholism for aldehyde dehydrogenase isozyme deficiency in Japan. Lancet 1982; 2 (8302): 827.

    Article  CAS  Google Scholar 

  11. Okayama A, Ueshima H, Yamakawa M, Kita Y . Low-Km aldehyde dehydrogenase deficiency does not influence the elevation of blood pressure by alcohol. J Hum Hypertens 1994; 8 (3): 205–208.

    CAS  Google Scholar 

  12. Tsuritani I, Ikai E, Date T, Suzuki Y, Ishizaki M, Yamada Y . Polymorphism in ALDH2-genotype in Japanese men and the alcohol-blood pressure relationship. Am J Hypertens 1995; 8 (11): 1053–1059.

    Article  CAS  Google Scholar 

  13. Ohsawa I, Kamino K, Nagasaka K, Ando F, Niino N, Shimokata H et al. Genetic deficiency of a mitochondrial aldehyde dehydrogenase increases serum lipid peroxides in community-dwelling females. J Hum Genet 2003; 48 (8): 404–409.

    Article  CAS  Google Scholar 

  14. Kato N, Takeuchi F, Tabara Y, Kelly TN, Go MJ, Sim X et al. Meta-analysis of genome-wide association studies identifies common variants associated with blood pressure variation in east Asians. Nat Genet 2011; 43 (6): 531–538.

    Article  CAS  PubMed  Google Scholar 

  15. Tsuchihashi-Makaya M, Serizawa M, Yanai K, Katsuya T, Takeuchi F, Fujioka A et al. Gene-environmental interaction regarding alcohol-metabolizing enzymes in the Japanese general population. Hypertens Res 2009; 32 (3): 207–213.

    Article  CAS  Google Scholar 

  16. Barany F . Genetic disease detection and DNA amplification using cloned thermostable ligase. Proc Natl Acad Sci USA 1991; 88 (1): 189–193.

    Article  CAS  Google Scholar 

  17. Excoffier L, Slatkin M . Maximum-likelihood estimation of molecular haplotype frequencies in a diploid population. Mol Biol Evol 1995; 12 (5): 921–927.

    CAS  Google Scholar 

  18. Dudbridge F . Likelihood-based association analysis for nuclear families and unrelated subjects with missing genotype data. Hum Hered 2008; 66 (2): 87–98.

    Article  PubMed  Google Scholar 

  19. Cui JS, Hopper JL, Harrap SB . Antihypertensive treatments obscure familial contributions to blood pressure variation. Hypertension 2003; 41 (2): 207–210.

    Article  CAS  PubMed  Google Scholar 

  20. Amamoto K, Okamura T, Tamaki S, Kita Y, Tsujita Y, Kadowaki T et al. Epidemiologic study of the association of low-Km mitochondrial acetaldehyde dehydrogenase genotypes with blood pressure level and the prevalence of hypertension in a general population. Hypertens Res 2002; 25 (6): 857–864.

    Article  CAS  Google Scholar 

  21. Saito K, Yokoyama T, Yoshiike N, Date C, Yamamoto A, Muramatsu M et al. Do the ethanol metabolizing enzymes modify the relationship between alcohol consumption and blood pressure? J Hypertens 2003; 21 (6): 1097–1105.

    Article  CAS  Google Scholar 

  22. Yamada Y, Sun F, Tsuritani I, Honda R . Genetic differences in ethanol metabolizing enzymes and blood pressure in Japanese alcohol consumers. J Hum Hypertens 2002; 16 (7): 479–486.

    Article  CAS  Google Scholar 

  23. Hines LM, Stampfer MJ, Ma J, Gaziano JM, Ridker PM, Hankinson SE et al. Genetic variation in alcohol dehydrogenase and the beneficial effect of moderate alcohol consumption on myocardial infarction. N Engl J Med 2001; 344 (8): 549–555.

    Article  CAS  Google Scholar 

  24. Takagi S, Iwai N, Yamauchi R, Kojima S, Yasuno S, Baba T et al. Aldehyde dehydrogenase 2 gene is a risk factor for myocardial infarction in Japanese men. Hypertens Res 2002; 25 (5): 677–681.

    Article  CAS  Google Scholar 

  25. Wada M, Daimon M, Emi M, Iijima H, Sato H, Koyano S et al. Genetic association between aldehyde dehydrogenase 2 (ALDH2) variation and high-density lipoprotein cholesterol (HDL-C) among non-drinkers in two large population samples in Japan. J Atheroscler Thromb 2008; 15 (4): 179–184.

    Article  CAS  Google Scholar 

  26. Guo YJ, Chen L, Bai YP, Li L, Sun J, Zhang GG et al. The ALDH2 Glu504Lys polymorphism is associated with coronary artery disease in Han Chinese: relation with endothelial ADMA levels. Atherosclerosis 2010; 211 (2): 545–550.

    Article  CAS  Google Scholar 

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Acknowledgements

This project was supported by grants from the National Natural Science Foundation of China (30771184 and 81000037) and the Natural Science Foundation of Shanghai (10ZR1425100).

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Authors and Affiliations

  1. State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Y Wang, Y Zhang, J Zhang, X Tang, Y Qian, P Gao & D Zhu

  2. Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Y Wang, Y Zhang, J Zhang, X Tang, Y Qian, P Gao & D Zhu

  3. Sino-French Research Center for Life Science and Genomics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Y Wang, Y Zhang & D Zhu

  4. Shanghai Key Laboratory of Vascular Biology, Shanghai Institute of Hypertension, Shanghai, China

    P Gao

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  1. Y Wang
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Correspondence to D Zhu.

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Wang, Y., Zhang, Y., Zhang, J. et al. Association of a functional single-nucleotide polymorphism in the ALDH2 gene with essential hypertension depends on drinking behavior in a Chinese Han population. J Hum Hypertens 27, 181–186 (2013). https://doi.org/10.1038/jhh.2012.15

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