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The combined impact of 12 common variants on hypertension in Japanese men, considering GWAS results


Genome-wide association studies have identified several polymorphisms that appear to be on hypertension-susceptible regions. We performed the current replication study in order to evaluate the association of these loci with hypertension in healthy Japanese males and then examined the combined effect of 12 independent variants. Overall, 735 Japanese men from two independent cohorts were recruited. Association with hypertension was assessed in 16 polymorphisms on 12 genes and 12 were chosen to evaluate the combined impact. Polymorphisms on the COMT, ATP2B1, CYP11A1 and the CSK genes were confirmed to be associated with hypertension and blood pressure (BP). Current findings also replicated previous results for the CYP11B2 and PTGIS genes. Although there were no significant associations found for other variants, our results suggested there was a combined impact for 12 loci. Individuals carrying more risk alleles had a higher risk of hypertension (P for the slope=0.002). Blood pressures also increased in conjunction with an increasing risk allele score (P for trend=7.84 × 10−6 and 1.85 × 10−5 for SBP and DBP, respectively). Our results confirmed the associations between hypertension or blood pressure and four gene variants. We also found a significant combined effect of the 12 gene loci.

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  1. Hajjar I, Kotchen JM, Kotchen TA . Hypertension: trends in prevalence, incidence, and control. Annu Rev Public Health 2006; 27: 465–490.

    Article  Google Scholar 

  2. Sekikawa A, Hayakawa T . Prevalence of hypertension, its awareness and control in adult population in Japan. J Hum Hypertens 2004; 18: 911–912.

    Article  CAS  Google Scholar 

  3. Cho YS, Go MJ, Kim YJ, Heo JY, Oh JH, Ban HJ et al. A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits. Nat Genet 2009; 41: 527–534.

    Article  CAS  Google Scholar 

  4. Newton-Cheh C, Johnson T, Gateva V, Tobin MD, Bochud M, Coin L et al. Genome-wide association study identifies eight loci associated with blood pressure. Nat Genet 2009; 41: 666–676.

    Article  CAS  Google Scholar 

  5. Org E, Eyheramendy S, Juhanson P, Gieger C, Lichtner P, Klopp N et al. Genome-wide scan identifies CDH13 as a novel susceptibility locus contributing to blood pressure determination in two European populations. Hum Mol Genet 2009; 18: 2288–2296.

    Article  CAS  Google Scholar 

  6. Angius A, Petretto E, Maestrale GB, Forabosco P, Casu G, Piras D et al. A new essential hypertension susceptibility locus on chromosome 2p24-p25, detected by genomewide search. Am J Hum Genet 2002; 71: 893–905.

    Article  Google Scholar 

  7. Zhu DL, Wang HY, Xiong MM, He X, Chu SL, Jin L et al. Linkage of hypertension to chromosome 2q14-q23 in Chinese families. J Hypertens 2001; 19: 55–61.

    Article  CAS  Google Scholar 

  8. Kamide K, Kokubo Y, Yang J, Tanaka C, Hanada H, Takiuchi S et al. Hypertension susceptibility genes on chromosome 2p24-p25 in a general Japanese population. J Hypertens 2005; 23: 955–960.

    Article  CAS  Google Scholar 

  9. Yamada Y, Kato K, Yoshida T, Yokoi K, Matsuo H, Watanabe S et al. Association of polymorphisms of ABCA1 and ROS1 with hypertension in Japanese individuals. Int J Mol Med 2008; 21: 83–89.

    CAS  PubMed  Google Scholar 

  10. Kamide K, Kokubo Y, Yang J, Matayoshi T, Inamoto N, Takiuchi S et al. Association of genetic polymorphisms of ACADSB and COMT with human hypertension. J Hypertens 2007; 25: 103–110.

    Article  CAS  Google Scholar 

  11. Kamide K, Kokubo Y, Fukuhara S, Hanada H, Yang J, Kada A et al. Protein tyrosine kinase 2beta as a candidate gene for hypertension. Pharmacogenet Genomics 2007; 17: 931–939.

    Article  CAS  Google Scholar 

  12. Song Y, Miyaki K, Araki J, Zhang L, Takahashi Y, Nakayama T et al. Influence of CYP11B2 gene polymorphism on the prevalence of hypertension and the blood pressure in Japanese men: interaction with dietary salt intake. J Nutrigenet Nutrigenomics 2008; 1: 252–258.

    Article  CAS  Google Scholar 

  13. Xie T, Ho SL, Ramsden D . Characterization and implications of estrogenic down-regulation of human catechol-O-methyltransferase gene transcription. Mol Pharmacol 1999; 56: 31–38.

    Article  CAS  Google Scholar 

  14. Hagen K, Pettersen E, Stovner LJ, Skorpen F, Holmen J, Zwart JA . High systolic blood pressure is associated with Val/Val genotype in the catechol-o-methyltransferase gene. The Nord-Trøndelag Health Study (HUNT). Am J Hypertens 2007; 20: 21–26.

    Article  CAS  Google Scholar 

  15. Annerbrink K, Westberg L, Nilsson S, Rosmond R, Holm G, Eriksson E . Catechol-O-methyltransferase val158-met polymorphism is associated with abdominal obesity and blood pressure in men. Metabolism 2008; 57: 708–711.

    Article  CAS  Google Scholar 

  16. Carafoli E . The Ca2+ pump of the plasma membrane. J Biol Chem 1992; 267: 2115–2118.

    CAS  PubMed  Google Scholar 

  17. Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ et al. Finding the missing heritability of complex diseases. Nature 2009; 461: 747–753.

    Article  CAS  Google Scholar 

  18. Wray NR, Goddard ME, Visscher PM . Prediction of individual genetic risk to disease from genome-wide association studies. Genome Res 2007; 17: 1520–1528.

    Article  CAS  Google Scholar 

  19. Yang J, Benyamin B, McEvoy BP, Gordon S, Henders AK, Nyholt DR et al. Common SNPs explain a large proportion of the heritability for human height. Nat Genet 2010; 42: 565–569.

    Article  CAS  Google Scholar 

  20. Lango H,, Palmer CN, Morris AD, Zeggini E, Hattersley AT et al. Assessing the combined impact of 18 common genetic variants of modest effect sizes on type 2 diabetes risk. Diabetes 2008; 57: 3129–3135.

    Article  CAS  Google Scholar 

  21. Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 2007; 447: 661–678.

    Article  Google Scholar 

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This study was supported by Grant-in-Aid for Scientific research (B) (19390173) from the Ministry of Education, Culture, Sports, Science and Technology (to Dr Miyaki) and Grant-in-Aid for Scientific research (C) (22590547) from Ministry of Education, Culture, Sports, Science and Technology (to Dr Muramatsu).

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Correspondence to K Miyaki.

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Miyaki, K., Htun, N., Song, Y. et al. The combined impact of 12 common variants on hypertension in Japanese men, considering GWAS results. J Hum Hypertens 26, 430–436 (2012).

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  • combined impact
  • polymorphism
  • blood pressure
  • genome-wide association study

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