Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Relationship between the regulatory region polymorphism of human tissue kallikrein gene and essential hypertension

Abstract

Ten alleles with length and nucleotide sequence variations were identified in the regulatory region of human tissue kallikrein gene. This present study aimed to study the polymorphisms of the regulatory region of human tissue kallikrein gene of the Chinese and investigate the relationship of the polymorphisms with essential hypertension. A case–control study was conducted in 200 hypertensive and 200 normotensive subjects of unrelated Chinese Han origin. All subjects were aged from 30 to 70 years and had no history of diabetes mellitus, kidney failure, or thyroid gland disease. The alleles were detected by polymerase chain reaction (PCR) and genotyping was performed with allele-specific oligonucleotide analysis (ASO). Data from the essential hypertensive and control subjects were statistically analysed by the Student's t-test and χ2-test. The age- and gender-matching of the groups were accurate. The case group and the control group were in Hardy–Weinberg equilibrium at this locus (cases, P=0.313; control subjects, P=0.457). There were nine alleles among the case and control groups, and the allele frequencies were found to be significantly different between cases and controls (χ2=25.701, P<0.001). The genotype frequencies were also significantly different (χ2=70.100, P<0.001) between these two groups. In conclusion, there are polymorphisms in the regulatory region of human tissue kallikrein gene in the Chinese Han people. Differences in both allele frequencies and genotype frequencies between these two groups have provided evidence towards the association of hypertension with the polymorphisms in this studied site.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Meneton P et al. Cardiovascular abnormalities with normal blood pressure in tissue kallikrein deficient mice. Proc Natl Acad Sci USA 2001; 98: 2634–2639.

    Article  CAS  Google Scholar 

  2. Campbell DJ . The kallikrein–kinin system in humans. Clin Exp Pharmacol Physiol 2001; 28(12): 1060–1065.

    Article  CAS  Google Scholar 

  3. Linz W et al. Contribution of kinins to the cardiovascular actions of angiotensin-converting enzyme inhibitors. Pharmacol Rev 1995; 47: 25–49.

    CAS  PubMed  Google Scholar 

  4. Siragy HM, Jaffa AA, Margolius HS, Carey RM . Renin–angiotensin system modulates renal bradykinin production. Am J Physiol 1996; 271: R1090–R1095.

    CAS  PubMed  Google Scholar 

  5. Harvey TJ et al. Tissue-specific expression patterns and fine mapping of the human kallikrein (KLK) locus on proximal 19q13.4. J Biol Chem 2000; 275: 37397–37406.

    Article  CAS  Google Scholar 

  6. Evans BA et al. Structure and chromosomal localization of the human renal kallikrein gene. Biochemistry 1988; 27: 3124–3129.

    Article  CAS  Google Scholar 

  7. Lifton RP . Molecular genetics of human blood pressure variation. Science 1996; 272: 676–680.

    Article  CAS  Google Scholar 

  8. Pravence M et al. Cosegregation of blood pressure with a kallikrein gene family polymorphism. Hypertension 1991; 17: 242–246.

    Article  Google Scholar 

  9. Wang J et al. Human tissue kallikrein induces hypotension in transgenic mice. Hypertension 1994; 23: 236–243.

    Article  CAS  Google Scholar 

  10. Berry TD et al. A gene for high urinary kallikrein may protect against hypertension in Utah kindreds. Hypertension 1989; 13: 3–8.

    Article  CAS  Google Scholar 

  11. Berge KE, Berg K . A Taq I RFLP at the human renal kallikrein (KLK1) locus. Clin Genet 1991; 40: 256.

    Article  CAS  Google Scholar 

  12. Berge KE, Berg K . No effect of Taq I polymorphism at the human renal kallikrein (KLK1) locus on normal blood pressure level or variability. Clin Genet 1993; 44: 196–202.

    Article  CAS  Google Scholar 

  13. Richards RI et al. Human glandular kallikrein genes genetic and physical mapping of the KLK1 locus using a highly polymorphic microsatellite PCR marker. Genomics 1991; 11: 77–82.

    Article  CAS  Google Scholar 

  14. Song Q, Chao J, Chao L . DNA polymorphisms in the 5′-flanking region of the human tissue kallikrein gene. Hum Genet 1997; 99: 727–734.

    CAS  PubMed  Google Scholar 

  15. Slim R et al. Loss-of-function polymorphism of the human kallikrein gene with reduced urinary kallikrein activity. J Am Soc Nephrol 2002; 13: 968–976.

    CAS  PubMed  Google Scholar 

  16. Lifton RP, Gharavi AG, Geller DS . Molecular mechanisms of human hypertension. Cell 2001; 104: 545–556.

    Article  CAS  Google Scholar 

  17. Staessen JA, Wang J, Bianchi G, Birkenhager WH . Essential hypertension. Lancet 2003; 361: 1629–1641.

    Article  Google Scholar 

  18. Clements JA . The glandular kallikrein family of enzyme: tissue specific expression and hormonal regulation. Endocr Rev 1989; 10: 393–419.

    Article  CAS  Google Scholar 

  19. Bhoola KD, Figueroa CD, Worthy K . Bioregulation of kinins: kallikreins, kininogens, and kininases. Pharmacol Rev 1992; 44: 1–80.

    CAS  PubMed  Google Scholar 

  20. Margolius HS . Tissue kallikreins and kinins: regulation and roles in hypertensive and diabetic diseases. Ann Rev Pharmacol Toxicol 1989; 29: 343–364.

    Article  CAS  Google Scholar 

  21. Overlack A . Antihypertensive effect of orally administered glandular kallikrein in essential hypertension. Results of double blind study. Hypertension 1981; 3: 118–121.

    Article  Google Scholar 

  22. Ogawa KT . Effects of orally administered glandular kallikrein on urinary kallikrein and prostaglandin excretion, plasma immunoreactive prostanoids and platelet aggregation in essential hypertension. Klin Wochenschr 1985; 63: 332–336.

    Article  CAS  Google Scholar 

  23. Xiong W, Chao J, Chao L . Muscle delivery of human tissue kallikrein gene reduces blood pressure in spontaneously hypertensive rats. Hypertension 1995; 25: 715–719.

    Article  CAS  Google Scholar 

  24. Harrap SB . Where are all the blood-pressure genes? Lancet 2003; 361: 2149–2151.

    Article  CAS  Google Scholar 

  25. Margolius HS, Horwitz D, Pisano JJ, Keiser HR . Urinary kallikrein in hypertension: Relationship to sodium intake and sodium-retaining steroid. Circ Res 1974; 35: 820–825.

    Article  CAS  Google Scholar 

  26. Cotton RG . Current methods of mutation detection. Mutat Res 1993; 285: 125–144.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank especially the participants in the study, and the doctors, nurses and administrative staff in hospitals who assisted with the study. This work was supported by the National Nature Science Foundation of China (No 39970275 to Wang Z, No 30070198 and 30470684 to Wan C) and CMB.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Z Wang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hua, H., Zhou, S., Liu, Y. et al. Relationship between the regulatory region polymorphism of human tissue kallikrein gene and essential hypertension. J Hum Hypertens 19, 715–721 (2005). https://doi.org/10.1038/sj.jhh.1001875

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.jhh.1001875

Keywords

This article is cited by

Search

Quick links