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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2013; 59(6): 12-24


Genetic predisposition to essential hypertension in children: analysis of 17 single nucleotide polymorphisms

Goncharov SV1, Gurianova VL2, Stroy DO1, Drevytska TI1, Kaplinskii SP2, Nastenko EA2, Litvinenko M2, Terletskiy RV2, Khaitovych MV2, Moibenko OO1, Dosenko VE1

  1. О.О. Bogomoletz Institute of Physiology, NAS ofUkraine, Kiev, Ukraine
  2. О.О. Bogomoletz National Medical University, Kiev, Ukraine
DOI: https://doi.org/10.15407/fz59.06.012


Abstract

Study of 17 single nucleotide polymorphisms has been performed to determine the factors of genetic predisposition to essential hypertension. Polymerase chain reaction (PCR) with subsequent analysis of restriction fragment length, allele specific PCR or real-time PCR was used for genotyping of 17 single nucleotide polymorphisms in 14 genes in 145 children with essential hypertension and 144 healthy persons with following complex multivariate statistical analysis. Two single nucleotide polymorphisms--MMP9 (C(-1562) --> T) and NOS3 (Glu298 --> Asp)--rs3918242 and rs1799983--were shown to represent the main independent effects with the highest predictive potential (77.1% as indicated by binary logistic regression and 74.6% testing accuracy shown by Multifactorial Dimensionality Reduction). MMP9 (C(-1562 --> T) and NOS3 (Glu298 --> Asp) potentially may be used to create predictive algorithm for determination of predisposition to arterial hypertension in children.

Keywords: single nucleotide polymorphism, genetics, hypertension, pediatrics

References

  1. Abilleira S., Bevan S., Markus H.S. The role of geneticvariants of matrix metalloproteinases in coronary andcarotid atherosclerosis . J. Med. Genet. 2006. 43. P.897-901. CrossRef PubMed PubMedCentral
  2.  
  3. AlShali K.Z., House A.A., Hanley A.J., Khan H.M.,Harris S.B., Zinman B., Mamakeesick M., Fenster A.,Spence J.D., Hegele R.A. Genetic variation in PPARGencoding peroxisome proliferatoractivated receptorgamma associated with carotid atherosclerosis . Stroke. 2004. 35. P.2036-2040. CrossRef PubMed
  4.  
  5. Bokkala S., Joseph S.K. Angiotensin IIinduced downregulationof inositol trisphosphate receptors in WB ratliver epithelial cells. Evidence for involvement of theproteasome pathway . J. Biol. Chem. 1997. 272. P.12454-12461. CrossRef PubMed
  6.  
  7. Buraczynska M., Grzebalska A., Spasiewicz D., OrlowskaG., Ksiazek A. Genetic polymorphisms of reninangiotensinsystem and progression of interstitial nephritis. Ann. Univ. Mariae Curie Sklodowska Med. 2002. 57. P.330-336. PubMed
  8.  
  9. Conen D., Cheng S., Steiner L.L., Buring J.E., RidkerP.M., Zee R.Y. Association of 77 polymorphisms in 52candidate genes with blood pressure progression and incidenthypertension: the Women's Genome Health Study. J. Hypertens. 2009. 27. P.476-483. CrossRef PubMed PubMedCentral
  10.  
  11. Dodel R.C., Bales K.R., Farlow M.R., Gasser T., PaulS.M., Du Y. Rapid detection of a pentanucleotide deletionpolymorphism in the human alpha2macroglobulin gene. Clin. Chem. 1999. 45. P.307-317. PubMed
  12.  
  13. Doris P.A. Hypertension genetics, single nucleotide polymorphisms,and the common disease: common varianthypothesis . Hypertension. 2002. 39. P.323-331. CrossRef PubMed
  14.  
  15. Dosenko V.E., Mykhal'chuk D.V., Zahorii V.Iu.,S.V. Goncharov, V.L. Gurianova, D.O. Stroy, T.I. Drevytska, S.P. Kaplinskii, E.A. Nastenko, M. Litvinenko, R.V. Terletskiy, M.V. Khaitovych, O.O. Moibenko, V.E. Dosenko 22 ISSN 02018489 Fiziol. zhurn., 2013, T. 59, N 6Khaitovych M.V., Moibenko O.O. Allelic polymorphismof genes encoding catalytic immunoproteasome subunitsand its functional meaning . Fiziol. Zh. 2005. 51. P.310.
  16.  
  17. Dosenko V.E., Zagorii V.Iu., Moibenko A.A. Effect of proteasomalproteolysis on NOsynthase activity in isolatedplatelets . Ukr. Biokhim. Zh. 2005. 77. P.39-43.
  18.  
  19. Ehret G.B., Morrison A.C., O'Connor A.A., Grove M.L.,Baird L., Schwander K., Weder A., Cooper R.S., RaoD.C., Hunt S.C., Boerwinkle E., Chakravarti A. Replicationof the Welcome Trust genomewide associationstudy of essential hypertension: The Family BloodPressure Program . Eur. J. Hum. Genet. 2008. 16. P.1507-1511. CrossRef PubMed PubMedCentral
  20.  
  21. Evans A.E., Poirier O., Kee F., Lecerf L., McCrumE., Falconer T., Crane J., O'Rourke D.F., Cambien F.Polymorphisms of the angiotensinconvertingenzymegene in subjects who die from coronary heart disease. Q. J. Med. 1994. 87. P.211-214. PubMed
  22.  
  23. Ghilardi G., Biondi M.L., DeMonti M., Bernini M., TurriO., Massaro F., Guagnellini E., Scorza R. Independentrisk factor for moderate to severe internal carotid arterystenosis: T786C mutation of endothelial nitric oxidesynthase gene . Clin. Chem. 2002. 48. P.989-993. PubMed
  24.  
  25. Goldberg A.L. Protein degradation and protection againstmisfolded or damaged proteins . Nature. 2003. 426. P.895-899. CrossRef PubMed
  26.  
  27. Goncharov S.V., Dosenko V.Ie., Khaitovych M.V.,Moibenko O.O. Allele polymorphism of genes codingproteasome subunits is associated with an enhanced riskfor arterial hypertension in adolescents . Fiziol. Zh. 2009. 55. P.310.
  28.  
  29. Hibi K., Ishigami T., Tamura K., Mizushima S., NyuiN., Fujita T., Ochiai H., Kosuge M., Watanabe Y., YoshiiY., Kihara M., Kimura K., Ishii M., Umemura S. Endothelialnitric oxide synthase gene polymorphism and acutemyocardial infarction . Hypertension. 1998. 32. P. 521-526. CrossRef PubMed
  30.  
  31. Hiura Y., Tabara Y., Kokubo Y., Okamura T., MikiT., Tomoike H., Iwai N. A genomewide associationstudy of hypertensionrelated phenotypes in a Japanesepopulation . Circ. J. 2010. 74(11). P.2353-2359. CrossRef PubMed
  32.  
  33. Johnson T., Gaunt T.R., Newhouse S.J. Blood pressureloci identified with a genecentric array . Amer. J. Hum.Genet. 2011. 89(6). P.688-700. CrossRef PubMed PubMedCentral
  34.  
  35. Jones G.T., Phillips V.L., Harris E.L., Rossaak J.I., vanRij A.M. Functional matrix metalloproteinase9polymorphism (C1562T) associated with abdominalaortic aneurysm . J. Vasc. Surg. 2003. 38. P.1363-1367. CrossRef  
  36. Kato N. Genetic analysis in human hypertension . Hypertens.Res. 2002. 25. P.319-27. CrossRef PubMed
  37.  
  38. Kupper N., Ge D., Treiber F.A., Snieder H. Emergenceof novel genetic effects on blood pressure and hemodynamicsin adolescence: the Georgia CardiovascularTwin Study . Hypertension. 2006. 47. P.948-954. CrossRef PubMed
  39.  
  40. Kurland L., Liljedahl U., Lind L. Hypertension and SNPgenotyping in antihypertensive treatment . Cardiovasc.Toxicol. 2005. 5. P.133-142. CrossRef  
  41. Kurtz T.W. Genome wide association studies will unlockthe genetic basis of hypertension: con side of the argument. Hypertension. 2010. 56. P.1021-1025. CrossRef PubMed
  42.  
  43. Lacolley P., Gautier S., Poirier O., Pannier B., CambienF., Benetos A. Nitric oxide synthase gene polymorphisms,blood pressure and aortic stiffness in normotensive andhypertensive subjects . J. Hypertens. 1998. 16. P.31-35. CrossRef PubMed
  44.  
  45. Lanfear D.E., Stolker J.M., Marsh S., Rich M.W., McLeodH.L. Genetic variation in the Btype natiuretic peptidepathway affects BNP levels . Drugs. Ther. 2007. 21. P.55-62.
  46.  
  47. Li N., Chen L., Yi F., Xia M., Li P.L. Saltsensitivehypertension induced by decoy of transcription factorhypoxiainducible factor1alpha in the renal medulla. Circ. Res. 2008. 102. P.1101-1108. CrossRef PubMed PubMedCentral
  48.  
  49. Lunn R.M., Langlois R.G., Hsieh L.L., ThompsonC.L., Bell D.A. XRCC1 polymorphisms: effects onaflatoxin B1DNA adducts and glycophorin A variantfrequency . Cancer. Res. 1999. 59. P.2557-2561. PubMed
  50.  
  51. Lurbe E., Cifkova R., Cruickshank J.K., Dillon M.J.,Ferreira I., Invitti C., Kuznetsova T., Laurent S., ManciaG., MoralesOlivas F., Rascher W., Redon J., SchaeferF., Seeman T., Stergiou G., Wuhl E., Zanchetti A.; EuropeanSociety of Hypertension. Management of high bloodpressure in children and adolescents: recommendationsof the European Society of Hypertension . J. Hypertens. 2009. 27. P.1719-1742. CrossRef PubMed
  52.  
  53. Madhani M., Okorie M., Hobbs A.J., MacAllister R.J.Reciprocal regulation of human soluble and particulateguanylate cyclases in vivo . Brit. J. Pharmacol. 2006. 149. P.797-801. CrossRef PubMed PubMedCentral
  54.  
  55. Maydannik V.G., Moskalenko V.F. Primary arterial hypertensionin children and adolescents. Kiev, 2007 P. 545.
  56.  
  57. Meirhaeghe A., Sandhu M.S., McCarthy M.I., deGroote P., Cottel D., Arveiler D., Ferrieres J., GrovesC.J., Hattersley A.T., Hitman G.A., Walker M., WarehamN.J., Amouyel P. Association between the T381Cpolymorphism of the brain natriuretic peptide gene andrisk of type 2 diabetes in human populations . Hum. Mol.Genet. 2007. 16. P.1343-1350. CrossRef PubMed
  58.  
  59. Melka M.G., Bernard M., Mahboubi A., AbrahamowiczM., Paterson A.D., Syme C., Lourdusamy A., SchumannG., Leonard G.T., Perron M., Richer L., VeilletteS., Gaudet D., Paus T., Pausova Z. . J. Clin. Endocrinol.Metab. 2012. 97(1). P.145-50. CrossRef PubMed
  60.  
  61. Miyamoto Y., Saito Y., Kajiyama N., YoshimuraM., Shimasaki Y., Nakayama M., Kamitani S., HaradaM., Ishikawa M., Kuwahara K., Ogawa E., HamanakaI., Takahashi N., Kaneshige T., Teraoka H., AkamizuT., Azuma N., Yoshimasa Y., Yoshimasa T., ItohH., Masuda I., Yasue H., Nakao K. Endothelial nitricoxide synthase gene is positively associated with essentialhypertension . Hypertension. 1998. 32. P.38. Endothelial nitric oxide synthase gene is positively associated with essential hypertension. Hypertension. 1998. 32. p.3–8. CrossRef PubMed
  62.  
  63. Nishikimi T., Maeda N., Matsuoka H. The role of natriureticpeptides in cardioprotection . Cardiovasc. Res. 2006. 69. P.318-328. CrossRef PubMed
  64.  
  65. Ocharoenrat P., Khantapura P. The role of geneticpolymorphisms in the promoters of the matrix metalloproteinase2 and tissue inhibitor of metalloproteinase2genes in head and neck cancer . Oral Oncol. 2006. 42. P.257-267. CrossRef PubMed
  66.  
  67. Dumont O., Loufrani L., Henrion D. Key Role of theNOPathway and Matrix Metalloprotease9 in HighBlood FlowInduced Remodeling of Rat ResistanceArteries . Arterioscler. Thromb. Vasc. Biol. 2007. 27. P.317-324. CrossRef PubMed PubMedCentral
  68.  
  69. Ozaki K., Sato H., Iida A. A functional SNP in PSMA6confers risk of myocardial infarction in the Japanesepopulation . Nat. Genet. 2006. 38. P.921-925. CrossRef PubMed
  70.  
  71. Page E.L., Chan D.A., Giaccia A.J., Levine M., RichardD.E. Hypoxiainducible factor1{alpha} stabilization innonhypoxic conditions: role of oxidation and intracellularascorbate depletion . Mol. Biol. Cell. 2008. 19. P.86-94. CrossRef PubMed PubMedCentral
  72.  
  73. Percy M.J., Mooney S.M., McMullin M.F., Flores A., LappinT.R., Lee F.S. A common polymorphism in theoxygendependent degradation (ODD) domain of hypoxiainducible factor1alpha (HIF1alpha) does not impairPro564 hydroxylation . Mol. Cancer 2003. 2. P.31. CrossRef PubMed PubMedCentral
  74.  
  75. Petrovic D., Bidovec M., Peterlin B. Gene polymorphismsof the reninangiotensinaldosterone system and essentialarterial hypertension in childhood . Folia Biol. 2002. 50. P.53-56.
  76.  
  77. Shastry B.S. SNPs: impact on gene function and phenotype. Methods Mol. Biol. 2009. 578. P.322. CrossRef PubMed
  78.  
  79. Shoji M., Yasujima M. Endothelial nitric oxide synthasegene and hypertension . Nippon. Rinsho 2000. 58. P.570-573. PubMed
  80.  
  81. Snieder H., Dong Y., Barbeau P., Harshfield G.A., DalageogouC., Zhu H., Carter N.D., Treiber F.A. Beta2adrenergic receptor gene and resting hemodynamicsin European and African American youth . Amer. J.Hypertens. 2002. 15. P.973-979. CrossRef  
  82. Snieder H., Harshfield G.A., Treiber F.A. Heritabilityof blood pressure and hemodynamics in African andEuropeanAmerican youth . Hypertension. 2003. 41. P.1196-1201. CrossRef PubMed
  83.  
  84. Staessen J.A., Asmar R., De Buyzere M., Imai Y., ParatiG., Shimada K., Stergiou G., Redon J., VerdecchiaP.; Participants of the 2001 Consensus Conference onAmbulatory Blood Pressure Monitoring. Task Force II:blood pressure measurement and cardiovascular outcome. Blood Press Monit. 2001 6 P. 355-357. CrossRef PubMed
  85.  
  86. Stangl V., Lorenz M., Meiners S., Ludwig A., BartschC., Moobed M., Vietzke A., Kinkel H.T., BaumannG., Stangl K. Longterm upregulation of eNOS andimprovement of endothelial function by inhibition ofthe ubiquitinproteasome pathway . FASEB J. 2004. 18. P.272-279. CrossRef PubMed
  87.  
  88. Strobl C., Malley J., Tutz G. An Introduction to recursivepartitioning: rationale, application and characteristics ofclassification and regression trees, bagging and randomforests . Psychol. Methods. 2009. 14(4). P.323-348. CrossRef PubMed PubMedCentral
  89.  
  90. Su W., Gao F., Lu J., Wu W., Zhou G., Lu S. Levels ofMatrix Metalloproteinase9 and Tissue Inhibitor ofMetalloproteinase1 mRNAs in Patients with PrimaryHypertension or Hypertensioninduced Atherosclerosis. J. Int. Med. Res. 2012. 40. P.986-994. CrossRef PubMed
  91.  
  92. Takashima N., Shioji K., Kokubo Y., Okayama A., GotoY., Nonogi H., Iwai N. Validation of the association betweenthe gene encoding proteasome subunit alpha type6 and myocardial infarction in a Japanese population. Circ. J. 2007. 71. P.495-498. CrossRef PubMed
  93.  
  94. Tsujita Y., Baba S., Yamauchi R., Mannami T., KinoshitaM., Yamamoto R., Katsuya T., Higaki J., OgiharaT., Ogata J., Iwai N. Association analyses between geneticpolymorphisms of endothelial nitric oxide synthasegene and hypertension in Japanese: The Suita Study . J.Hypertens. 2001. 19. P.1941-1948. CrossRef PubMed
  95.  
  96. Vinasco J., Fraile A., Nieto A., Beraun Y., Pareja E., MataranL., Martin J. Analysis of Lmp and Tap Polymorphismsby Polymerase Chain Reaction Restriction FragmentLength Polymorphism in Rheumatoid Arthritis . Ann.Rheum. Dis. 1998. 57. P.33-37. CrossRef PubMed PubMedCentral
  97.  
  98. Wang X.L., Sim A.S., Wang M.X., Murrell G.A., TrudingerB., Wang J. Genotype dependent and cigarette specificeffects on endothelial nitric oxide synthase gene expressionand enzyme activity . FEBS Lett. 2000. 471. P.45-50. CrossRef  
  99. Yang H.C., Liang Y.J., Wu Y.L., Chung C.M., ChiangK.M., Ho H.Y., Ting C.T., Lin T.H., Sheu S.H., TsaiW.C., Chen J.H., Leu H.B., Yin W.H., Chiu T.Y., ChenC.I., Fann C.S., Wu J.Y., Lin T.N., Lin S.J., Chen Y.T., ChenJ.W., Pan W.H. Genomewide association study of youngonsethypertension in the Han Chinese population ofTaiwan . PLoS One. 2009. 4(5). P.54-59. CrossRef PubMed PubMedCentral
  100.  
  101. Yasmin, Wallace S., McEniery C.M., Dakham Z., PusalkarP., MakiPetaja K., Ashby M.J., Cockcroft J.R., WilkinsonI.B. Matrix Metalloproteinase9 (MMP9), MMP2,and Serum Elastase Activity Are Associated With SystolicHypertension and Arterial Stiffness . Arterioscler.Thromb. Vasc. Biol. 2005. 25. P.372-378. CrossRef PubMed
  102.  
  103. Ye S. Influence of matrix metalloproteinase genotype oncardiovascular disease susceptibility and outcome. .Cardiovasc. Res. 2006. 69. P.636-645. CrossRef PubMed
  104.  
  105. Zappia M., Manna I., Serra P., Cittadella R., AndreoliV., La Russa A., Annesi F., Spadafora P., Romeo N., NicolettiG., Messina D., Gambardella A., Quattrone A. Increasedrisk for Alzheimer disease with the interaction ofMPO and A2M polymorphisms . Arch. Neurol. 2004. 61. P.341-344. CrossRef PubMed
  106.  
  107. Zervoudaki A., Economou E., Stefanadis C., PitsavosC., Tsioufis K., Aggeli C., Vasiliadou K., Toutouza M.,Toutouzas P. Plasma levels of active extracellular matrixmetalloproteinases 2 and 9 in patients with essential hypertensionbefore and after antihypertensive treatment. J. Hum. Hypertens. 2003. 17. P.119-124. CrossRef PubMed
  108.  
  109. Zhang W., Meng H., Li Z.H., Shu Z., Ma X., Zhang B.X.Regulation of STIM1, storeoperated Ca2+ influx, andnitric oxide generation by retinoic acid in rat mesangialcells . Amer. J. Physiol. Renal Physiol. 2007. 292. P.1054-1064. CrossRef PubMed
  110.  
  111. ZorcPleskovic R., Bidovec M., Bregar D., MilutinovicA., Terzic R., Teran N. The ScaI gene polymorphismof the atrial natriuretic factor and essential arterialhypertension in childhood . Coll. Antropol. 2004. 28. P.617-621. PubMed

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