Association of renin-angiotensin system and natriuretic peptide receptor A gene polymorphisms with hypertension in a Hellenic population

Abstract

Introduction. Hypertension results from the interaction of genetic and environmental factors. Since the renin-angiotensin and the natriuretic peptide systems contribute to blood pressure regulation, variations in the relative genes are candidates for the development of hypertension.

Materials and methods. In 194 hypertensives and 304 controls of Hellenic origin, the possible association between the (CA)_n repeat polymorphism of angiotensinogen (AGT), the 250 bp insertion/deletion (I/D) of angiotensin-converting enzyme (ACE), the tetranucleotide repeat polymorphism (TCTG)_n of renin, and the (CT)_n repeat polymorphism of the natriuretic peptide receptor A (NPRA) and hypertension was assessed.

Results. No association between AGT and NPRA polymorphisms and hypertension was observed. The presence of ID or DD genotype of ACE was associated with an increased risk for hypertension compared with the II genotype (OR: 1.782 [95% CI: 1.032—3.077]), whereas the LL genotype of the renin gene was associated with a decreased risk compared with the SS genotype (OR: 0.174 [95% CI: 0.044—0.689]). However, after adjustment for confounding factors only the latter association remained.

Conclusions. In the present study conducted in a homogeneous Hellenic population, no associations betweenAGT,ACE, and NPRA gene polymorphisms and hypertension were found. The presence of a significant negative association between the LL polymorphism of the renin gene and hypertension requires further confirmation.

Keywords

Hellenic population hypertension natriuretic peptide receptor A polymorphisms renin-angiotensin

Get full access to this article

View all access options for this article.

References

Pickering G. Hyperpiesis: high blood pressure without evident cause: essential hypertension. BMJ 1965;2:1021-6.

Beevers G. , Lip GYH , O'Brien E. ABC of hypertension: the pathophysiology of hypertension. BMJ 2001;322:912-6.

Marteau JB , Zaiou M. , Siest G. , Visvikis-Siest S. Genetic determinants of blood pressure regulation. J Hypertens 2005; 23:2127-43.

Nebert DW

Polymorphisms in drug-metabolizing enzymes: what is their clinical relevance and why do they exist?

Am J Hum Genet 1997 ;60:265-71.

Fytili P. , Giannatou E. , Papanikolaou V. et al. Association of repeat polymorphisms in the estrogen receptor α, β, and androgen receptor genes with knee osteoarthritis. Clin Genet 2005;68:268-77.

Isa MN , Boyd E. , Morrison N. , Harrap S. , Clauser E. , Connor JM Assignment of the human angiotensinogen gene to chromosome 1q42-q43 by non-isotopic in situ hybridization. Genomics 1990;8:598-600.

Caulfield M. , Lavender P. , Newell-Price J. et al. Linkage of the angiotensinogen gene locus to human essential hypertension in African Caribbeans. J Clin Invest 1995;96:687-92.

Hata A. , Namikawa C. , Sasaki M. et al. Angiotensinogen as a risk factor for essential hypertension in Japan. J Clin Invest 1994;93:1285-7.

Morise T. , Takeuchi Y. , Takeda R. Rapid detection and prevalence of variants of the angiotensinogen gene in patients with essential hypertension. J Int Med 1995;237:175-80.

10.

Bennet CL , Schrader AP , Morris BJ Cross-sectional analysis of Met235 to Thr variant of angiotensinogen gene in severe, familial hypertension. Biochem Biophys Res Commun 1993;197:833-9.

11.

Morgan L. , Broughton Pipkin F. , Kalsheker N. DNA polymorphisms and linkage disequilibrium in the angiotensinogen gene. Hum Genet 1996;98:194-8.

12.

Niu T. , Chen X. , Xu X. Angiotensin converting enzyme gene insertion/deletion polymorphism and cardiovascular disease therapeutic implications. Drugs 2002 ;62:977-93.

13.

Zee RY , Lou YK , Griffiths LR , Morris BJ Association of a polymorphism of the angiotensin I-converting enzyme gene with essential hypertension. Biochem Biophys Res Commun 1992;184:9-15.

14.

Duru K. , Farrow S. , Wang JM , Lockette W. , Kurtz T. Frequency of a deletion polymorphism in the gene for angiotensin converting enzyme is increased in African-Americans with hypertension. Am J Hypertens 1994;7:759-62.

15.

Fornage M. , Amos CI , Kardia S. , Sing CF , Turner ST , Boerwinkle E. Variation in the region of the angiotensin-converting enzyme gene influences interindividual differences in blood pressure levels in young white males . Circulation 1998;97:1773-9.

16.

Barbalic M. , Skaric-Juric T. , Cambien F. et al. Gene polymorphisms of the renin-angiotensin system and early development of hypertension. Am J Hypertens 2006;19:837-42.

17.

Sugiyama T. , Morita H. , Kato N. et al. Lack of sex-specific effects on the association between angiotensin-converting enzyme gene polymorphism and hypertension in Japanese. Hypertens Res 1999;22:55-9.

18.

Gui-yan W. , Yan-hua W. , Qun X. et al. Associations between RAS gene polymorphisms, enviromental factors and hypertension in Mongolian people. Eur J Epidemiol 2006;21: 287-92.

19.

Di Pasquale P. , Canizzaro S. , Paterna S. Does angiotensin-converting enzyme gene polymorphism affect blood pressure? Findings after 6 years of follow-up in healthy subjects . Eur J Heart Fail 2004;6:11-6.

20.

Castellano M. , Glorioso N. , Cusi D. et al. Molecular Genetic Study Group of the Italian Society of Hypertension. Genetic polymorphisms of the renin-angiotensin-aldosterone system and arterial hypertension in the Italian population: the GENIPER project . J Hypertens 2003;21:1853-60.

21.

Gu XX , Spaepen M. , Guo C. et al. Lack of association between the I/D polymorphism of the angiotensin-converting enzyme gene and essential hypertension in a Belgian population. J Hum Hypertens 1994;8:683-5.

22.

Schmidt S. , van Hooft IM , Grobbee DE , Ganten D. , Ritz E. Polymorphism of the angiotensin I converting enzyme gene is apparently not related to high blood pressure: Dutch Hypertension and Offspring Study. J Hypertens 1993;11:345-8.

23.

Bae Y. , Park C. , Han J. et al. Interaction between GNB3 C825T and ACE I/D polymorphisms in essential hypertension in Koreans. J Hum Hypertens 2007;21:159-66.

24.

Mondry A. , Loh M. , Pengbo L. , Zhu AL , Nagel M. Polymorphisms of the insertion/deletion ACE and M235T AGT genes and hypertension: surprising new findings and meta-analysis of data. BMC Nephrology 2005;6:1-11.

25.

Vassilikioti S. , Doumas M. , Douma S. et al. Angiotensin converting enzyme gene polymorphism is not related to essential hypertension in a Greek population . Am J Hypertens 1996;9:700-02.

26.

Rapp JP , Wang S. -M, Dene H. A genetic polymorphism in the renin gene of Dahl rats consegregates with blood pressure. Science 1989;243:542-4.

27.

Kurtz TW , Simonet L. , Kabra PM , Wolfe S. , Chan L. , Hjelle BL Cosegregation of the renin alleles of the spontaneously hypertensive rat with an increase in blood pressure. J Clin Invest 1990;85:1328-32.

28.

Frossard PM , Malloy MJ , Lestrigant GG , Kane JP Haplotypes of the human renin gene associated with essential hypertension and stroke. J Hum Hypertens 2001;15:49-55.

29.

Hasimu B. , Nakayama T. , Mizutani Y. et al. A novel variable number of tandem repeat polymorphism of the renin gene and essential hypertension. Hypertens Res 2003;26:473-7.

30.

Naber CK , Siffert W. Genetics of human arterial hypertension. Minerva Med 2004;95:347-56.

31.

Knowles J. , Erickson L. , Guy V. , Sigel C. , Wilder J. , Maeda N. Common variations in noncoding regions of the human natriuretic peptide receptor A gene have quantitative effects. Hum Genet 2003;112:62-70.

32.

Nakayama T. , Soma M. , Takahashi T. et al. Nucleotide sequence of the 59-flanking region of the type A human natriuretic peptide receptor gene and association analysis using a novel microsatellite in essential hypertension . Am J Hypertens 1999;12:1144-8.

33.

Sarzani R. , Dessi-Fulgheri P. , Salvi F. et al. A novel promoter variant of the natriuretic peptide clearance receptor gene is associated with lower atrial natriuretic peptide and higher blood pressure in obese hypertensives. J Hypertens 1999;17:1301-05.

34.

Aoi N. , Soma M. , Nakayama T. et al. Variable number of tandem repeat of the 5'-flanking region of type-C human natriuretic peptide receptor gene influences blood pressure levels in obesity-associated hypertension. Hypertens Res 2004;27:711-6.