Correlation of Renin Angiotensin System (RAS) Candidate Gene Polymorphisms with Response to Ramipril in Patients with Essential Hypertension

Overview

Journal J Postgrad Med

Specialty General Medicine

Date 2014 Dec 17

PMID 25511213

Citations 12

Authors

S Gupta

I Chattopadhyaya

B K Agrawal

P K Sehajpal

R K Goel

Affiliations

Soon will be listed here.

Abstract

Background: The renin-angiotensin system (RAS) is an important facet of blood pressure regulation physiology. Treatment of essential hypertension targets the RAS using Angiotensin Converting Enzyme Inhibitors (ACEIs). However, ACEIs are not uniformly effective and show inter-individual pharmacodynamic variations.

Aim: To assess the correlation between genetic polymorphisms in the genes coding for RAS components (angiotensin converting enzyme (ACE I/D), α-adducin (ADD1) and β1 -adrenoreceptor (β1-ADR)) and response to Ramipril.

Materials And Methods: We recruited 120 patients with essential hypertension who were administered Ramipril monotherapy initially, followed by combination therapy, if needed, based on their responses. Relationship between genotypes of the three candidate genes and decrease in the blood pressure (BP) was analyzed.

Results: One hundred and six patients were evaluable at the end of the study period and 21 different genotypes were observed among them. Seven of them were classified as responders after 8 weeks and at the end of 12 weeks, an additional 77 (72.64%) were deemed responders. 19/22 non-responders were treated with combination therapy and 7/19 (36.84%) showed a response to the same. There was a significant difference between the proportions of responders and non-responders among the genotypes of the ADD1 and β1-ADR genes (P=0.005 and 0.003, respectively). The best predictors of response to Ramipril 5 mg daily were the II/GG/SS, II/TG/SS, II/GG/SG, ID/GG/SS, ID/GG/SG and ID/TT/SS and DD/GG/SS; II/GG/GG, II/TT/SG, ID/TG/SG, ID/TT/SG, DD/GG/SG and DD/GG/GG were moderately predictive and II/TT/SS, II/TG/GG, ID/TG/GG, DD/TG/SG and DD/TG/GG were poorly predictive of response.

Discussion: Variable responses to Ramipril may be the result of genetic factors.

Conclusion: Pre-prescription genotyping may help individualize treatment.

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References

Scharplatz M, Puhan M, Steurer J, Bachmann L . What is the impact of the ACE gene insertion/deletion (I/D) polymorphism on the clinical effectiveness and adverse events of ACE inhibitors?--Protocol of a systematic review. BMC Med Genet. 2004; 5:23. PMC: 518966. DOI: 10.1186/1471-2350-5-23. View

Chobanian A, Bakris G, Black H, Cushman W, Green L, Izzo Jr J . Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003; 42(6):1206-52. DOI: 10.1161/01.HYP.0000107251.49515.c2. View

Ueda S, MEREDITH P, Morton J, Connell J, Elliott H . ACE (I/D) genotype as a predictor of the magnitude and duration of the response to an ACE inhibitor drug (enalaprilat) in humans. Circulation. 1998; 98(20):2148-53. DOI: 10.1161/01.cir.98.20.2148. View

Manunta P, Burnier M, DAmico M, Buzzi L, Maillard M, Barlassina C . Adducin polymorphism affects renal proximal tubule reabsorption in hypertension. Hypertension. 1999; 33(2):694-7. DOI: 10.1161/01.hyp.33.2.694. View

Miller S, Dykes D, Polesky H . A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988; 16(3):1215. PMC: 334765. DOI: 10.1093/nar/16.3.1215. View

Joshi S, Parikh R . India--diabetes capital of the world: now heading towards hypertension. J Assoc Physicians India. 2007; 55:323-4. View

Manunta P, Cusi D, Barlassina C, Righetti M, Lanzani C, DAmico M . Alpha-adducin polymorphisms and renal sodium handling in essential hypertensive patients. Kidney Int. 1998; 53(6):1471-8. DOI: 10.1046/j.1523-1755.1998.00931.x. View

Manunta P, Bianchi G . Pharmacogenomics and pharmacogenetics of hypertension: update and perspectives--the adducin paradigm. J Am Soc Nephrol. 2006; 17(4 Suppl 2):S30-5. DOI: 10.1681/ASN.2005121346. View

Fragoso J, Rodriguez-Perez J, Perez-Vielma N, Martinez-Rodriguez N, Vargas-Alarcon G . Beta1 adrenergic receptor polymorphisms Arg389Gly and Ser49Gly in the Amerindian and Mestizo populations of Mexico. Hum Biol. 2006; 77(4):515-20. View

10.

Shin M, Chung E, Kim H, Park K, Nam H, Kweon S . Alpha-adducin Gly460Trp polymorphism and essential hypertension in Korea. J Korean Med Sci. 2004; 19(6):812-4. PMC: 2816309. DOI: 10.3346/jkms.2004.19.6.812. View

11.

Agrawal S, Singh V, Tewari S, Sinha N, Ramesh V, Agarwal S . Angiotensin-converting enzyme gene polymorphism in coronary artery disease in north India. Indian Heart J. 2004; 56(1):44-6. View

12.

Tiret L, Rigat B, Visvikis S, Breda C, Corvol P, Cambien F . Evidence, from combined segregation and linkage analysis, that a variant of the angiotensin I-converting enzyme (ACE) gene controls plasma ACE levels. Am J Hum Genet. 1992; 51(1):197-205. PMC: 1682892. View

13.

Humma L, Terra S . Pharmacogenetics and cardiovascular disease: impact on drug response and applications to disease management. Am J Health Syst Pharm. 2002; 59(13):1241-52. DOI: 10.1093/ajhp/59.13.1241. View

14.

Johnson J, Zineh I, Puckett B, McGorray S, Yarandi H, Pauly D . Beta 1-adrenergic receptor polymorphisms and antihypertensive response to metoprolol. Clin Pharmacol Ther. 2003; 74(1):44-52. DOI: 10.1016/S0009-9236(03)00068-7. View

15.

Levin M, Marullo S, Muntaner O, Andersson B, Magnusson Y . The myocardium-protective Gly-49 variant of the beta 1-adrenergic receptor exhibits constitutive activity and increased desensitization and down-regulation. J Biol Chem. 2002; 277(34):30429-35. DOI: 10.1074/jbc.M200681200. View

16.

Karlsson J, Lind L, Hallberg P, Michaelsson K, Kurland L, Kahan T . Beta1-adrenergic receptor gene polymorphisms and response to beta1-adrenergic receptor blockade in patients with essential hypertension. Clin Cardiol. 2004; 27(6):347-50. PMC: 6654438. DOI: 10.1002/clc.4960270610. View

17.

Staessen J, Wang J, Ginocchio G, Petrov V, Saavedra A, Soubrier F . The deletion/insertion polymorphism of the angiotensin converting enzyme gene and cardiovascular-renal risk. J Hypertens. 1998; 15(12 Pt 2):1579-92. DOI: 10.1097/00004872-199715120-00059. View

18.

Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F . An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest. 1990; 86(4):1343-6. PMC: 296868. DOI: 10.1172/JCI114844. View

19.

Ferrandi M, Salardi S, Tripodi G, Barassi P, Rivera R, Manunta P . Evidence for an interaction between adducin and Na(+)-K(+)-ATPase: relation to genetic hypertension. Am J Physiol. 1999; 277(4):H1338-49. DOI: 10.1152/ajpheart.1999.277.4.H1338. View