Heart and vascular remodeling in essential hypertension and type 2 diabetes is dependent on genetic polymorphisms

Abstract

Aim: To study heart and vascular remodeling in essential hypertension (EH) and concomitant type 2 diabetes mellitus (DM2) with respect to genetic polymorphism of the angiotensin II receptor type 1 (AGTR1) gene and peroxisome proliferator-activated receptor-γ2 (PPARγ2).

Methods: Biochemical blood analysis, echocardiographic evaluation of mitral diastolic blood flow and tissue Doppler spectral modes, reactive hyperemia, color Doppler mapping.

Results: Patients with A/C and C/C genotypes of the AGTR1 gene had higher blood pressure, more pronounced metabolic disorders, a larger left ventricle (LV), higher myocardial mass index left ventricle, and a greater intima media thickness (IMT), with a lower rate of endothelium-dependent vasodilation (EDVD) compared to the A/A genotype. Patients with the Pro/Pro genotype of PPARγ2 had higher levels of blood pressure, larger LVs, greater IMT, pulse wave velocity, and a lower rate of EDVD compared to the Pro/Ala and Ala/Ala genotypes. Patients with the Pro/Pro genotype had significantly more pronounced dyslipidemia and insulin resistance than patients with other PPARγ2 genotypes.

Conclusion: The polymorphism of genetic markers AGTR1 and PPARγ2 in patients with EH and concomitant DM2 was associated with the development of comorbidity. Different genotypes of specific genes alter the severity of cardiovascular remodeling and metabolic disorders.

Keywords


Essential hypertension / type 2 diabetes comorbidity / genetic polymorphism / heart and vascular remodeling

References

[1] Mettimano M,Ianni A,Migneco A.AGT and AT1R gene polymorphism in hypertensive heart disease..In J Clin Pract2002;56:574-7

[2] Martínez-Gómez LE,Martínez-Nava GA,Parra E,Espinoza-Rojo M,Piza-Roma LF,Burguete-García AI.A replication study of the IRS1, CAPN10, TCF7L2, and PPARG gene polymorphisms associated with type 2 diabetes in two different populations of Mexico..Ann Hum Genet2011;75:612-20

[3] Czarnecka D,Stolarz K,Kieć-Wilk B.Genetic factors in hypertension. Angiotensin-converting enzyme polymorphism..Kardiol Pol2004;61:1-10

[4] Wang X,Dong Y,Snieder H.Effects of angiotensinogen and angiotensin II type I receptor genes on blood pressure and left ventricular mass trajectories in multiethnic youth..Twin Res Hum Genet2006;9:393-402

[5] Mettimano M,Ianni A,Migneco A.AGT and AT1R gene polymorphism in hypertensive heart diseas..Int J Clin Pract2002;56:574-7

[6] Berry C,Fennell J,Dominiczak AF.Oxidative stress and vascular damage in hypertension..Curr Opin Nephrol Hypertens2001;10:247-55

[7] de Denus S,Dubé MP,Lepage S,Gossard D,Racine N,Lavoie J,Turgeon J.Effects of AGTR1 A1166C gene polymorphism in patients with heart failure treated with candesartan..Ann Pharmacother2008;42:925-32

[8] Grundy SM,Daniels SR,Eckel RH,Gordon DJ,Savage PJ,Spertus JA.Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institue Scientific Statement..Circulation2005;112:2735-52

[9] Colwell JA.Type 2 diabetes, Pre-diabetes, and the metabolic syndrome..JAMA2011;306:215

[10] Saad MF,Selby J,Jinagouda S,Zaccaro D,Savage PJ.Insulin resistance and hypertension: the Insulin Resistance Atherosclerosis study..Hypertention2004;43:1324-31

[11] Chen Z,Chambers KT,Mitra MS,McDonald WG,Kletzien RF.Insulin resistance and metabolic derangements in obese mice are ameliorated by a novel peroxisome proliferator-activated receptor γ-sparing thiazolidinedione..J Biol Chem2012;287:23537-48 PMCID:PMC3390629

[12] Yen CJ,Negri C,Brown KA,Burns DK,Shuldiner AR.Molecular scanning of the human peroxisome proliferator activated receptor gamma (hPPAR gamma) gene in diabetic Caucasians: identification of a Pro12Ala PPAR gamma 2 missense mutation..Biochem Biophys Res Commun1997;241:270-4

[13] Palatini P,Dorigatti F,Santonastaso M,Papparella I,Semplicini A.Angiotensin II type 1 receptor gene polymorphism predicts development of hypertension and metabolic syndrome..Am J Hypertens2009;22:208-14

[14] Lehtonen J,Daviet L.Angiotensin II type 1 receptor 1166 polymorphism A to C increases mRNA stability and steady-state levels..Circulation2006;114:190

[15] Jiang Z,Yu F.Association of angiotension II type 1 receptor gene polymorphism with essentional hypertension..Chin Med J (Engl)2001;114:1249-51

[16] Motavallian A,Vaseghi G,Amini M.Association between PRO12ALA polymorphism of the PPAR-γ2 gene and type 2 diabetes mellitus in Iranian patients..Indian J Hum Genet2013;19:239-44 PMCID:PMC3758733

[17] Ohshima K,Horiuchi M.Role of peroxisome proliferator-activated receptor-γ in vascular inflammation..Int J Vasc Med2012;2012:508416

[18] He W.PPARγ2 polymorphism and human health..PPAR Res2009;2009:849538

[19] Zhang F,Zheng S.Peroxisome proliferator-activated receptor-γ cross-regulation of signaling events implicated in liver fibrogenesis..Cell Signal2012;24:596-605

[20] Gawrieh S,Komorowski R,Charlton M,Langefeld CD.Genetic variation in the peroxisome proliferator activated receptor-gamma gene is associated with histologically advanced NAFLD..Dig Dis Sci2012;57:952-7