Aim: The study objective was to examine the association of hypertension in the Lebanese population with three renin–angiotensin system gene polymorphisms (RAS): angiotensin-converting enzyme (ACE), angiotensinogen (AGT) and angiotensin-receptor type 1 (AT1R).
Methods: A total of 270 subjects (124 hypertensive vs 146 normotensive) were genotyped for ACE insertion (I)/deletion (D), AGT (M235T), and AT1R (A1166C) gene polymorphisms by polymerase chain reaction and restriction fragment length polymorphism.
Results: The studied genes showed no deviation from Hardy–Weinberg equilibrium. No association could be reported with the ACE I/D polymorphism, although the D allele frequency was high (77%) in patients. AGT TT genotype prevalence was found to be lower in hypertensive versus normotensive subjects (p < 0.0001). AT1R CC and AC genotypes were significantly more frequent in hypertensive than normotensive subjects (p < 0.0001).
Conclusion: The first conducted study on the RAS gene polymorphisms in Lebanese hypertensive patients demonstrated a possible association of the AGT T and AT1R C alleles with hypertension.
ChangYPLiuXKimJDIkedaMALaytonMRWederAB. Multiple genes for essential-hypertension susceptibility on chromosome 1q. Am J Hum Genet2007; 80: 253–264.
2.
AgarwalRAndersenMJ. Blood pressure recordings within and outside the clinic and cardiovascular events in chronic kidney disease. Am J Nephrol2006; 26: 503–510.
3.
IshikawaJKarioKEguchiKMorinariMHoshideSIshikawaS. Regular alcohol drinking is a determinant of masked morning hypertension detected by home blood pressure monitoring in medicated hypertensive patients with well-controlled clinic blood pressure: the Jichi Morning Hypertension Research (J-MORE) study. Hypertens Res2006; 29: 679–686.
4.
JeunemaitreXSoubrierFKotelevtsevYVLiftonRPWilliamsCSCharruA. Molecular basis of human hypertension: role of angiotensinogen. Cell1992; 71: 169–180.
5.
ZhuXChangYPYanDWederACooperRLukeA. Associations between hypertension and genes in the renin-angiotensin system. Hypertension2003; 41: 1027–1034.
6.
BarleyJBlackwoodAMillerMMarkanduNDCarterNDJeffreyS. Angiotensin converting enzyme gene I/d polymorphism, blood pressure and the renin-angiotensin system in Caucasian and Afro-Caribbean people. J Hum Hypertens1996; 10: 31–35.
7.
ThomasGNTomlinsonBChanJCSandersonJECockramCSCritchleyJA. Renin-angiotensin system gene polymorphisms, blood pressure, dyslipidemia, and diabetes in Hong Kong Chinese: a significant association of the ace insertion/deletion polymorphism with type 2 diabetes. Diabetes Care2001; 24: 356–361.
8.
GesangLLiuGGenWQiuCZhuomaCZhuangL. Angiotensin-converting enzyme gene polymorphism and its association with essential hypertension in a Tibetan population. Hypertens Res2002; 25: 481–485.
TodorokiMMinamiJIshimitsuTOhruiMMatsuokaH. Relation between the angiotensin-converting enzyme insertion/deletion polymorphism and blood pressure in Japanese male subjects. J Hum Hypertens2003; 17: 713–718.
11.
AgachanBIsbirTYilmazHAkogluE. Angiotensin converting enzyme I/D, angiotensinogen T174M-M235T and angiotensin II type 1 receptor A1166C gene polymorphisms in Turkish hypertensive patients. Exp Mol Med2003; 35: 545–549.
12.
Di PasqualePCannizzaroSPaternaS. Does angiontensin-converting enzyme gene polymorphism affect blood pressure? Findings after 6 years of follow up in healthy subjects. Eur J Heart Fail2004; 6: 11–16.
13.
IsmailMAkhtarNNasirMFirasatSAyubQKhaliqS. Association between the angiotensin-converting enzyme gene insertion/deletion polymorphism and essential hypertension in young Pakistani patients. J Biochem Mol Biol2004; 37: 552–555.
14.
TripathiGDharmaniPKhanFSharmaRKPandirikkalVAgrawalS. Prevalence of ACE DD genotype among North Indian end stage renal disease patients. BMC Nephrol2006; 7: 15–22.
15.
BaeYParkCHanJHongYSongHShinE. Interaction between GNB3 C825T and ACE I/D polymorphisms in essential hypertension in Koreans. J Hum Hypertens2007; 21: 159–166.
16.
DzidaGSobstylJPuzniakAGolonPMosiewiczJHanzlikJ. Polymorphisms of angiotensin-converting enzyme and angiotensin II receptor type 1 genes in essential hypertension in a Polish population. Med Sci Monit2001; 7: 1236–1241.
17.
PereiraACMotaGFCunhaRSHerbenhoffFLMillJGKreigerJE. Angiotensinogen 235T allele ‘dosage’ is associated with blood pressure phenotypes. Hypertension2003; 41: 25–30.
18.
WuSJChiangFTChenWJLiuPHHsuKLHwangJJ. Three single-nucleotide polymorphisms of the angiotensinogen, and risk of hypertension: single locus genotype vs. haplotype analysis. Physiol Genomics2004; 17: 79–86.
19.
MondryALohMLiuPZhuANagelM. Polymorphisms of the insertion/deletion ACE and M235T AGT genes and hypertension: surprising new findings and meta-analysis of data. BMC Nephrol2005; 6: 1–12.
20.
ProcopciucLMPopDZdrengheaDJebeleanuG. Genetic analysis of angiotensinogen gene polymorphisms (M235T and T174M) in Romanian patients with essential arterial hypertension. Rom J Intern Med [Abstract] 2005; 43: 61–71.
21.
SayYHLingKHDuraisamyGIsaacSRosliR. Angiotensinogen M235T gene variants and its association with essential hypertension and plasma renin activity in Malaysian subjects: a case control study. BMC Cardiovasc Disord2005; 5: 7–17.
22.
RijnMJBosMJIsaacsAYazdanpanahMArias-VasquezAStrickerBH. Polymorphisms of the renin-angiotensin system are associated with blood pressure, atherosclerosis and cerebral white matter pathology. J Neurol Neurosurg Psychiatry [Abstract] 2007; 78: 1083–1087.
23.
VassilikiotiSDoumasMDoumaSPetidisKKaragiannisABalaskaK. Angiotensin converting enzyme gene polymorphism is not related to essential hypertension in a Greek population. Am J Hypertens1996; 9: 700–702.
24.
SchmidtSVan HooftIMGrobbeeDEGantenDRitzE. Polymorphism of the angiotensin I converting enzyme gene is apparently not related to high blood pressure: Dutch hypertension and offspring study. J Hypertens1993; 11: 345–348.
25.
FuentesRMPerolaMNissinenATuomilehtoJ. ACE gene and physical activity, blood pressure, and hypertension: a population study in Finland. J Appl Physiol2002; 92: 2508–2512.
26.
TamakiSNakamuraYTsujitaYNozakiAAmamotoKKadowakiT. Polymorphism of the angiotensin converting enzyme gene and blood pressure in a Japanese general population (the Shigaraki study). Hypertens Res2002; 25: 843–848.
27.
LeeKBKimUK. Angiotensinogen and Angiotensin II Type I receptor gene polymorphism in patients with autosomal dominant polycystic kidney disease: effect on hypertension and ESRD. Yonsei Med J2003; 44: 641–647.
28.
RennerWNauckMWinkelmannBRHoffmannMMScharnaglHMayerV. Association of angiotensinogen haplotypes with angiotensinogen levels but not with blood pressure or coronary artery disease; the Ludwigshafen risk and cardiovascular health study. J Mol Med2005; 83: 235–239.
29.
OrtleppJRMetrikatJMevissenVScmitzFAlbrechtMMaya-PelzerP. Relation between the angiotensinogen (AGT) M235T gene polymorphism and blood pressure in a large homogeneous study population. J Hum Hypertens2003; 17: 555–559.
30.
NairKShaliaKKAshavaidTFDalalJJ. Coronary heart disease, hypertension, and angiotensinogen gene variants in Indian population. J Clin Lab Anal2003; 17: 141–146.
31.
SchmitzSRitzE. Genetics of the renin-angiotensin system and renal disease: a progress report. Curr Opin Nephrol Hypertens1997; 6: 146–151.
32.
GainerJVHunleyTEKonVNadeauJHMuldowneyJA3rdBrownNJ. Angiotensin II type 1 receptor polymorphism in African Americans lower frequency of the C1166 variant. Biochem Mol Biol Int1997; 43: 227–231.
33.
Rodriguez-PerezJCRodriguez-EsparragonFJHernandez-PereraOFiuza-PerezMDAnabitarte-PrietoALosada-CabreraA. Effects of the angiotensinogen gene M235T and A(-6)G variants on blood pressure and other vascular risk factors in a Spanish population. J Hum Hypertens2000; 14: 789–793.
34.
OnoKMannamiTBabaSYasuiNOgiharaTIwaiN. Lack of association between angiotensin II type 1 receptor gene polymorphisms and hypertension in Japanese. Hypertens Res2003; 26: 131–134.
35.
BayoumiRSimsekMYahyaTBendictSAl-HinaiAAl-BarwaniH. Insertion-deletion polymorphism in the angiotensin-converting enzyme (ACE) gene among Sudanese, Somalis, Emiratis and Omanis. Hum Biol2006; 78: 103–108.
36.
SipahiTBudakMŞenSAyAŞenerS. Association between ACE gene insertion (I)/deletion (D) polymorphism and primary hypertension in Turkish patients of Trakya region. Biotech and Biotech Equip2006; 20: 104–108.
37.
BehravanJNaghibiMMazloomiMAHassanyM. Polymorphism of angiotensin II type 1 receptor gene in essential hypertension in Iranian population. DARU2006; 14: 82–86.
38.
PilbrowAPPalmerBRFramptonCMYandleTGTroughtonRWCampbellE. Angiotensinogen M235T and T174M gene polymorphisms in combination doubles the risk of mortality in heart failure. Hypertension2007; 49: 322–327.
39.
SaabYBGardPROverallADJ. The geographic distribution of ACE II genotype: a novel finding. Genetic Research2007; 89: 245–257.
40.
RigatBHubertCAlhenc-GelasFCambienFCorvolPSoubrierF. An insertion/deletion polymorphism of the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest1990; 86: 1343–1346.
41.
RichardsBSkoletskyJShuberAPBalfourRSternRCDorkinHR. Multiplex PCR amplification from CFTR gene using DNA prepared from buccal brushes/swabs. Hum Mol Genet1993; 2: 159–163.
42.
SeryOVojtovaVZvolskyP. The association study of DRD2, ACE, and AGT gene polymorphism and metamphetamine dependence. Physiol Res2001; 50: 43–50.
43.
OdawaraMMatsunumaAYamashitaK. Mystyping frequency of the angiotensin-converting enzyme gene polymorphism and an improved method for its avoidance. Hum Genet1997; 100: 163–166.
44.
RyuSKChoEYParkHYImEKJangYSShimGJ. Renin-angiotensin-aldosterone system (RAAS) gene polymorphism as a risk factor of coronary instent testenosis. Younsei Medical J2002; 43: 461–472.
45.
McCullaghPNelderJA. Generalized linear models. London: Chapman & Hall, 1989.
46.
CrawleyMJ. GLIM for ecologists. Oxford UK: Blackwell Scientific Publications, 1993.
47.
BrennerHBlettnerM. Controlling for continuous confounders in epidemiologic research. Epidemiology1997; 8: 429–434.
48.
DanserAHSchunkertH. Renin-angiotensin system gene polymorphisms: potential mechanisms for their association with cardiovascular diseases. Eur J Pharmacol. [Review]2000; 410: 303–316.
49.
SpieringWKroonAAFuss-LejeuneMMDaemenMJDe LeeuwPW. Angiotensin II sensitivity is associated with the angiotensin II type 1 receptor A(1166)C polymorphism in essential hypertensives on a high sodium diet. Hypertension2000; 36: 411–416.
50.
MiyamaNHasegawaYSuzukiMHidaWKazamaI, R H. Investigation of major genetic polymorphisms in the renin-angiotensin-aldosterone system in subjects with young-onset hypertension selected by a targeted-screening system at university. Clin Exp Hypertens2007; 29: 61–67.
51.
FaulFErdfelderEBuchnerALangA-G. Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behavior Research Methods2009; 41: 1149–1160.
52.
DaviesHTOCrombieIKTavakoliM. When can odds ratios mislead?BMJ1998; 316: 989–991.
