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Role of two angiotensinogen polymorphisms in blood pressure variation

Abstract

Genetic analysis of hypertension has yielded inconsistent results, making it difficult to draw clear conclusions regarding the impact of specific variants on blood pressure regulation. Among the most studied of the candidate genes for blood pressure regulation is angiotensinogen (AGT), but as with other candidate loci associations with blood pressure have been inconsistent. We examined the contributions of two AGT polymorphisms (T174M and M235T) to detect the effects of each on blood pressure variation, using single-site and two-site analyses. We analysed data from a study of 177 subjects from Accra, Ghana. We observed significant single-locus associations of the T174M polymorphism with average systolic (SBP) and diastolic blood pressure (DBP) when age was used as a covariate (P<0.001 and P=0.010, respectively). Also, we observed a significant association of the M235T polymorphism with SBPs and DBPs (P<0.001 and P=0.014, respectively). Finally, we observed a simultaneous significant association of the two polymorphisms with SBP and DBP (P<0.001 and P=0.026, respectively), although the two-loci model is not significantly better than either single-locus model. However, for SBP the two-loci model is marginally better (P=0.08 in comparison to both single-locus models). These results suggest that variants at these two AGT sites together, in conjunction with age, may be significantly associated with elevated SBP, whereas the single-site models are as good models of DBP. It is possible that earlier inconsistent results with these AGT polymorphisms with hypertension in African-derived populations may have resulted from an ‘incomplete’ model in the different study populations. Given the inconclusive nature of our two-loci results, this possibility requires further investigation.

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References

  1. Halushka MK et al. Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis. Nat Genet 1999; 22: 239–247.

    Article  CAS  PubMed  Google Scholar 

  2. Moore JH, Williams SM . New strategies for identifying gene–gene interactions in hypertension. Ann Med 2002; 34: 88–95.

    Article  CAS  PubMed  Google Scholar 

  3. Williams SM, Haines JL, Moore JH . The use of animal models in the study of complex disease: all else is never equal or why do so many human studies fail to replicate animal findings? BioEssays 2004; 26: 170–179.

    Article  CAS  PubMed  Google Scholar 

  4. Hata A et al. Angiotensinogen as a risk factor for essential hypertension in Japan. J Clin Invest 1994; 93: 1285–1287.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Inoue I et al. A nucleotide substitution in the promoter of human angiotensinogen is associated with essential hypertension and affects basal transcription in vitro. J Clin Invest 1997; 99: 1786–1797.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Jeunemaitre X et al. Molecular basis of human hypertension: role of angiotensinogen. Cell 1992; 71: 169–180.

    Article  CAS  PubMed  Google Scholar 

  7. Caulfield M et al. Linkage of the angiotensinogen gene to essential hypertension. N Engl J Med 1994; 330: 1629–1633.

    Article  CAS  PubMed  Google Scholar 

  8. Bloom LJ et al. Association of the angiotensinogen gene to serum angiotensinogen in blacks and whites. Hypertension 1997; 29: 1078–1082.

    Article  Google Scholar 

  9. Williams SM et al. Combinations of variations in multiple genes are associated with hypertension. Hypertension 2000; 36: 2–6.

    Article  CAS  PubMed  Google Scholar 

  10. Yarows SA, Brook RD . Measurement variation among 12 electronic home blood pressure monitors. Am J Hypertens 2000; 13: 276–282.

    Article  CAS  PubMed  Google Scholar 

  11. Mufunda J et al. Comparison of the Omron HEM-713C automated blood pressure monitor with a standard ausculatory method using a mercury manometer. Cent Afr J Med 1996; 42: 230–232.

    CAS  PubMed  Google Scholar 

  12. Seber GAF . Linear Regression Analysis. Wiley: New York, 1977.

    Google Scholar 

  13. Zhao JH, Curtis D, Sham PC . Model-free analysis and permutation tests for allelic associations. Hum Hered 2000; 50: 133–139.

    Article  CAS  PubMed  Google Scholar 

  14. Ishigami T et al. Angiotensinogen gene polymorphism near transcription start site and blood pressure: role of a T-to-C transition at intron I. Hypertension 1999; 34: 430–434.

    Article  CAS  PubMed  Google Scholar 

  15. Rotimi C et al. Polymorphisms of renin–angiotensin genes among Nigerians, Jamaicans, and African Americans. Hypertension 1996; 27: 558–563.

    Article  CAS  PubMed  Google Scholar 

  16. Forrester T et al. Angiotensinogen and blood pressure among blacks: findings from a community survey in Jamaica. J Hypertens 1996; 14: 315–321.

    Article  CAS  PubMed  Google Scholar 

  17. Rotimi C et al. Angiotensinogen gene in human hypertension. Lack of an association of the 235T allele among African Americans. Hypertension 1994; 24: 591–594.

    Article  CAS  PubMed  Google Scholar 

  18. Robinson MT et al. AGT and RH blood group polymorphisms affect blood pressure and lipids in Afro-Caribbeans. J Hum Hypertens 2004; 18: 351–363.

    Article  CAS  PubMed  Google Scholar 

  19. Caulfield M et al. Linkage of the angiotensinogen gene locus to human essential hypertension in African Caribbeans. J Clin Invest 1995; 96: 687–692.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Zhu X et al. Associations between hypertension and genes in the renin–angiotensin system. Hypertension 2003; 41: 1027–1034.

    Article  CAS  PubMed  Google Scholar 

  21. Zhu X et al. Linkage disequilibrium and haplotype diversity in the genes of the renin–angiotensin system: findings from the family blood pressure program. Genome Res 2003; 13: 173–181.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Jeunemaitre X et al. Haplotypes of angiotensinogen in essential hypertension. Am J Hum Genet 1997; 60: 1448–1460.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the National Institutes of Health (HL0321, HL65234).

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Correspondence to S M Williams.

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Robinson, M., Williams, S. Role of two angiotensinogen polymorphisms in blood pressure variation. J Hum Hypertens 18, 865–869 (2004). https://doi.org/10.1038/sj.jhh.1001768

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