Genetic Analysis of Kallikrein-Kinin System in the Korean Hypertensives

  • Kang, ByungYong (Research Institute for Life Science, Sahmyook University) ;
  • Bae, Joon Seol (Department of Biochemistry, College of Science, Yonsei University) ;
  • Lee, Kang Oh (Department of Life Science, Sahmyook University)
  • Published : 2004.03.01

Abstract

The kallikrein-kinin system affects regulation of blood pressure, and genes encoding for the components of this system have been considered as good candidates for hypertension. To evaluate the relationship between genetic polymorphisms of candidate genes involved in this system and hypertension, we performed case-control studies using genetic markers in Korean normotensives and hypertensives, respectively. By association study, there was a marginal association with hypertension in AA genotype distribution of A1789G polymorphism in the hKLK1 gene (P=0.0754). Thus, this genetic polymorphism may weakly contribute to the susceptibility to hypertension in Koreans. We also observed that significant linkage disequilibrium exists among three polymorphic sites in the hKLK1 gene studied, suggesting that the three genetic polymorph isms can be useful as genetic markers in clinical association studies. Further studies using larger sample sizes and more genetic markers will be needed to clarify genetic influence of kallikrein-kinin system for hypertension.

Keywords

References

  1. Berge KE, Bakken A, Bohn M, Erikssen J, and Berg K (1997) Analyses of mutations in the human renal kallikrein (hKLK1) gene and their possible relevance to blood pressure regulation and risk of myocardial infarction. Clin Genet 52: 86-95 https://doi.org/10.1111/j.1399-0004.1997.tb02524.x
  2. Berge KE and Berg K (1993) No effect of Taq I polymorphism at the human renal kallikrein (KLK1) locus on normal blood pressure level or variability. Clin Genet 44: 196-202 https://doi.org/10.1111/j.1399-0004.1993.tb03879.x
  3. Berry TD, Hasstedt SJ, Hunt SC, Wu LL, Smith JB, Ash KO, Kuida H, and Williams RR (1989) a gene for high urinary kallikrein may protect against hypertension in Utah kindreds. Hypertension 13: 3-8 https://doi.org/10.1161/01.HYP.13.1.3
  4. Bhoola KD, Figueroa CD, and Worthy K (1992) Bioregulation of kinins: kallikreins, kininogens, and kininases. Pharmacol Rev 44: 1-80
  5. Braun A, Kammerer S, Bohme E, Muller B, and Roscher AA (1995a) Identification of polymorphic sites of the human bradykinin $B_2$ receptor gene: full length cDNA, genomic organization and identification of the regulatory region. Biochem Biophys Res Commun 211: 226-233 https://doi.org/10.1006/bbrc.1995.1800
  6. Braun A, Kammerer S, Bohme E, Muller B, and Roscher AA (1995b) Identification of polymorphic sites of the human bradykinin $B_2$ receptor gene. Biochem Biophys Res Commun 211: 234-240 https://doi.org/10.1006/bbrc.1995.1801
  7. Cheung PP, Cannizzaro LA, and Colman RW (1992) Chromosomal mapping of human kininogen gene (KNG) to 3q26 to qter. Cytogenet Cell Genet 59: 24-26 https://doi.org/10.1159/000133192
  8. Cheung PP, Kunapuli SP, Scott CF, Wachtfogel YT, and Colman RW (1993) Genetic basis of total kininogen deficiency in Williams' trait. J Biol Chem 268: 23361-23365
  9. Chung DW, Fujikawa K, McMullen BA, and Davie EW (1986) Human plasma prekallikrein, a zymogen to a serine protease that contains four tandem repeats. Biochemistry 25: 2410-2417 https://doi.org/10.1021/bi00357a017
  10. Clements JA (1994) The human kallikrein gene family: a diversity of expression and function. Mol Cell Endocrinol 99: C1-C6 https://doi.org/10.1016/0303-7207(94)90138-4
  11. Evans BA, Yun ZY, Close JA, Tregear GW, Kitamura N, Nakanishi C, Callen DF, Baker E, Hyland VJ, Sutherland GR, and Richards RI (1988) Structure and chromosomal localization of the human renal kallikrein gene. Biochemistry 27: 3124-3129 https://doi.org/10.1021/bi00409a003
  12. Fong D, Smith DI, and Hsieh WT (1991) The human kininogen gene (KNG) mapped to chromosome $3q26{\to}qter$ by analysis of somatic cell hybrids using the polymerase chain reaction. Hum Genet 87: 189-192 https://doi.org/10.1007/BF00204179
  13. Friend LR, Morris BJ, Gaffney PT, and Griffiths LR (1996) Examination of the role of nitric oxide synthase and renal kallikrein as candidate genes for essential hypertension. Clin Exp Pharmacol Physiol 23: 564-566 https://doi.org/10.1111/j.1440-1681.1996.tb02780.x
  14. Gainer JV, Brown NJ, Bachvarova M, Bastien L, Maltais I, Marceau F, and Bachvarov DR (2000) Altered frequency of a promoter polymorphism of the kinin $B_2$ receptor gene in hypertensive African-Americans. Am J Hypertens 13: 1268-1273 https://doi.org/10.1016/S0895-7061(00)01215-2
  15. Harvey TJ, Hooper JD, Myers SA, Stephenson SA, Ashworth LK, and Clements JA (2000) Tissue-specific expression patterns and fine mapping of the human kallikrein (KLK) locus on proximal 19q13.4. J Biol Chem 275: 37397-37406 https://doi.org/10.1074/jbc.M004525200
  16. Hess JF, Borkowski JA, Young GS, Strader CD, and Ransom RW (1992) Cloning and pharmacological characterization of a human bradykinin (BK-2) receptor. Biochem Biophys Res Commun 184: 260-268 https://doi.org/10.1016/0006-291X(92)91187-U
  17. Hill WG and Robertson A (1968) Linkage disequilibrium of finite populations. Theor Appl Genet 38: 226-231 https://doi.org/10.1007/BF01245622
  18. Kammerer S, Broun A, Arnold N, and Roscher AA (1995) The human bradykinin $B_2$ receptor gene. Biochem Biophys Res Commun 21: 234-240
  19. Kang BY, Kim KT, Eo HS, Lee KH, Hong SS, Shin JH, and Lee CC (2000) Association between genetic variation of the insulin receptor gene and essential hypertension in the Korean population. Korean J Biol Sci 4: 87-90 https://doi.org/10.1080/12265071.2000.9647528
  20. Kang BY and Lee KO (2003) Genetic polymorphisms of t-PA and PAI-1 genes in the Korean population. Korean J Biol Sci 7: 249-253 https://doi.org/10.1080/12265071.2003.9647711
  21. Kitamura N, Kitagawa H, Fukushima D, Takaqaki Y, Miyata T, and Nakaniski S (1985) Structural organization of the human kininogen gene and a model for its evolution. J Biol Chem 260: 8610-8617
  22. Kurtz TW and Spence MA (1993) Genetics of essential hypertension. Am J Med 94: 77-84 https://doi.org/10.1016/0002-9343(93)90124-8
  23. Lewontin RC (1964) The interaction of selection and linkage. I. General considerations: heterotic models. Genetics 49: 49-67
  24. Margolius HS (1989) Tissue kallikreins and kinins: regulation and roles in hypertensive and diabetic diseases. Annu Rev Pharmacol Toxicol 29: 343-364 https://doi.org/10.1146/annurev.pa.29.040189.002015
  25. Margolius HS (1995) Kallikreins and kinins: some unanswered questions about system characteristics and role in human disease. Hypertension 26: 221-229 https://doi.org/10.1161/01.HYP.26.2.221
  26. Margolius HS (1996) Kallikreins and kinins: molecular characteristics and cellular and tissue responses. Diabetes 45 Suppl 1: S14-S19
  27. Margolius HS, Horwitz D, Pisano JJ, and Keiser HR (1974) Urinary kallikrein excretion in hypertensive man: relationships to sodium intake and sodium-retaining steroids. Circ Res 35: 820-825 https://doi.org/10.1161/01.RES.35.6.820
  28. Meneton P, Bloch-Faure M, Hagege A, Ruetten H, Huang W, Bergaya S, Ceiler D, Gerhing D, Martins I, Salmon G, Boulanger CM, Nussberger J, Crozatier B, Gasc JM, Heudes D, Bruneval P, Doetschman T, Menard J, and Alhenc-Gelas F (2001) Cardiovascular abnormalities with normal blood pressure in tissue kallikrein deficient mice. Proc Natl Acad Sci USA 98: 2634-2639 https://doi.org/10.1073/pnas.051619598
  29. Pravenec M, Kren V, Kunes J, Scicli AG, Carretero OA, Simonet L, and Kurtz TW (1991) Cosegregation of blood pressure with a kallikrein gene family polymorphism. Hypertension 17: 242-246 https://doi.org/10.1161/01.HYP.17.2.242
  30. Proud D and Kaplan AP (1988) Kinin formation mechanisms and role in inflammatory disorders. Annu Rev Immunol 6: 49-83 https://doi.org/10.1146/annurev.iy.06.040188.000405
  31. Sham PC and Curtis D (1995) Monte Carlo tests for associations between diseases and alleles at highly polymorphic loci. Ann Hum Genet 59: 97-105 https://doi.org/10.1111/j.1469-1809.1995.tb01608.x
  32. Schneck KA, Hess JF, Stonesifer GY, and Ransom RW (1994) Bradykinin $B_1$ receptors in rabbit aorta smooth muscle cells in culture. Eur J Pharmacol 266: 277-282 https://doi.org/10.1016/0922-4106(94)90137-6
  33. Slim R, Torremocha F, Moreau T, Pizard A, Hunt SC, Vuagnat A, Williams GH, Gauthier F, Jeunemaitre X, and Alhenc-Gelas F (2002) Loss-of-function polymorphism of the human kallikrein gene with reduced urinary kallikrein activity. J Am Soc Nephrol 13: 968-976
  34. Zinner SH, Margolius HS, Rosner B, Keiser HR, and Kass EH (1976) Familial aggregation of urinary kallikrein concentration in childhood: relation to blood pressure, race and urinary electrolytes. Am J Epidemiol 104: 124-132 https://doi.org/10.1093/oxfordjournals.aje.a112282