Effects of Antihypertensive Drugs and Gene Variants in the Renin-Angiotensin System
Many genes and environmental factors are involved in the pathogenesis of hypertension, but the exact cause of essential hypertension has not yet been clarified. Gene polymorphism of the renin-angiotensin system (RAS) is one of the candidates. In the current study, we examined whether there was a cor...
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Published in | Hypertension Research Vol. 24; no. 4; pp. 463 - 467 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
The Japanese Society of Hypertension
2001
|
Subjects | |
Online Access | Get full text |
ISSN | 0916-9636 1348-4214 1348-4214 |
DOI | 10.1291/hypres.24.463 |
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Abstract | Many genes and environmental factors are involved in the pathogenesis of hypertension, but the exact cause of essential hypertension has not yet been clarified. Gene polymorphism of the renin-angiotensin system (RAS) is one of the candidates. In the current study, we examined whether there was a correlation between the gene polymorphisms in RAS and either the choice of antihypertensive drugs or their efficacy. Subjects with essential hypertension (n=299) were recruited from among the outpatients of Osaka University Hospital and provided their informed consent for genetic analysis. Physicians freely chose the antihypertensive drugs and adjusted its dose until the patient’s blood pressure was well controlled. The efficacy of each antihypertensive drug was estimated using the following formula: ΔBP=BP 1 (before treatment) - BP 2 (after treatment)/BP 1×100(%). Gene variants in RAS were determined using PCR or PCR-RFLP (restriction fragment of polymorphism). The gene polymorphism of RAS were not associated with ΔSBP or ΔDBP. However, the mean ΔSBP in subjects with a deletion homozygote of the angiotensin converting enzyme gene (ACE/DD) was significantly lower (p<0.05) than that in patients with an insertion/allele of the ACE gene. The gene polymorphisms of RAS did not significantly affect the choice of antihypertensive drugs. Even though gene polymorphism in the renin angiotensin system was not a major factor in the anti-hypertensive therapy, the determination of genotype might be of help in the management of essential hypertension. (Hypertens Res 2001; 24: 463-467) |
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AbstractList | Many genes and environmental factors are involved in the pathogenesis of hypertension, but the exact cause of essential hypertension has not yet been clarified. Gene polymorphism of the renin-angiotensin system (RAS) is one of the candidates. In the current study, we examined whether there was a correlation between the gene polymorphisms in RAS and either the choice of antihypertensive drugs or their efficacy. Subjects with essential hypertension (n=299) were recruited from among the outpatients of Osaka University Hospital and provided their informed consent for genetic analysis. Physicians freely chose the antihypertensive drugs and adjusted its dose until the patient's blood pressure was well controlled. The efficacy of each antihypertensive drug was estimated using the following formula: ABP=BP 1 (before treatment) - BP 2 (after treatment)/BP 1 x 100 (%). Gene variants in RAS were determined using PCR or PCR-RFLP (restriction fragment of polymorphism). The gene polymorphisms of RAS were not associated with delta SBP or ADBP. However, the mean ASBP in subjects with a deletion homozygote of the angiotensin converting enzyme gene (ACE/DD) was significantly lower (p<0.05) than that in patients with an insertion I allele of the ACE gene. The gene polymorphisms of RAS did not significantly affect the choice of antihypertensive drugs. Even though gene polymorphism in the renin angiotensin system was not a major factor in the antihypertensive therapy, the determination of genotype might be of help in the management of essential hypertension.Many genes and environmental factors are involved in the pathogenesis of hypertension, but the exact cause of essential hypertension has not yet been clarified. Gene polymorphism of the renin-angiotensin system (RAS) is one of the candidates. In the current study, we examined whether there was a correlation between the gene polymorphisms in RAS and either the choice of antihypertensive drugs or their efficacy. Subjects with essential hypertension (n=299) were recruited from among the outpatients of Osaka University Hospital and provided their informed consent for genetic analysis. Physicians freely chose the antihypertensive drugs and adjusted its dose until the patient's blood pressure was well controlled. The efficacy of each antihypertensive drug was estimated using the following formula: ABP=BP 1 (before treatment) - BP 2 (after treatment)/BP 1 x 100 (%). Gene variants in RAS were determined using PCR or PCR-RFLP (restriction fragment of polymorphism). The gene polymorphisms of RAS were not associated with delta SBP or ADBP. However, the mean ASBP in subjects with a deletion homozygote of the angiotensin converting enzyme gene (ACE/DD) was significantly lower (p<0.05) than that in patients with an insertion I allele of the ACE gene. The gene polymorphisms of RAS did not significantly affect the choice of antihypertensive drugs. Even though gene polymorphism in the renin angiotensin system was not a major factor in the antihypertensive therapy, the determination of genotype might be of help in the management of essential hypertension. Many genes and environmental factors are involved in the pathogenesis of hypertension, but the exact cause of essential hypertension has not yet been clarified. Gene polymorphism of the renin-angiotensin system (RAS) is one of the candidates. In the current study, we examined whether there was a correlation between the gene polymorphisms in RAS and either the choice of antihypertensive drugs or their efficacy. Subjects with essential hypertension (n=299) were recruited from among the outpatients of Osaka University Hospital and provided their informed consent for genetic analysis. Physicians freely chose the antihypertensive drugs and adjusted its dose until the patient's blood pressure was well controlled. The efficacy of each antihypertensive drug was estimated using the following formula: ABP=BP 1 (before treatment) - BP 2 (after treatment)/BP 1 x 100 (%). Gene variants in RAS were determined using PCR or PCR-RFLP (restriction fragment of polymorphism). The gene polymorphisms of RAS were not associated with delta SBP or ADBP. However, the mean ASBP in subjects with a deletion homozygote of the angiotensin converting enzyme gene (ACE/DD) was significantly lower (p<0.05) than that in patients with an insertion I allele of the ACE gene. The gene polymorphisms of RAS did not significantly affect the choice of antihypertensive drugs. Even though gene polymorphism in the renin angiotensin system was not a major factor in the antihypertensive therapy, the determination of genotype might be of help in the management of essential hypertension. Many genes and environmental factors are involved in the pathogenesis of hypertension, but the exact cause of essential hypertension has not yet been clarified. Gene polymorphism of the renin-angiotensin system (RAS) is one of the candidates. In the current study, we examined whether there was a correlation between the gene polymorphisms in RAS and either the choice of antihypertensive drugs or their efficacy. Subjects with essential hypertension (n=299) were recruited from among the outpatients of Osaka University Hospital and provided their informed consent for genetic analysis. Physicians freely chose the antihypertensive drugs and adjusted its dose until the patient’s blood pressure was well controlled. The efficacy of each antihypertensive drug was estimated using the following formula: ΔBP=BP 1 (before treatment) - BP 2 (after treatment)/BP 1×100(%). Gene variants in RAS were determined using PCR or PCR-RFLP (restriction fragment of polymorphism). The gene polymorphism of RAS were not associated with ΔSBP or ΔDBP. However, the mean ΔSBP in subjects with a deletion homozygote of the angiotensin converting enzyme gene (ACE/DD) was significantly lower (p<0.05) than that in patients with an insertion/allele of the ACE gene. The gene polymorphisms of RAS did not significantly affect the choice of antihypertensive drugs. Even though gene polymorphism in the renin angiotensin system was not a major factor in the anti-hypertensive therapy, the determination of genotype might be of help in the management of essential hypertension. (Hypertens Res 2001; 24: 463-467) |
Author | SUGIMOTO, Ken HATANAKA, Yasuko MOTONE, Motoharu ASAI, Takashi OHISHI, Mitsuru RAKUGI, Hiromi OGIHARA, Toshio FUKUDA, Masayuki KATSUYA, Tomohiro HIGAKI, Jitsuo IWASHIMA, Yoshio FU, Yuxiao |
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References_xml | – reference: 29. Ohishi M, Rakugi H, Ogihara T: Association between a deletion polymorphism of the angiotensin-converting-enzyme gene and left ventricular hypertrophy. N Engl J Med 1994; 331: 1097-1098. – reference: 8. Xu X, Rogus JJ, Terwedow HA, et al: An extreme-sib-pair genome scan for genes regulating blood pressure. Am J Hum Genet 1999; 64: 1694-1701. – reference: 31. Hunt SC, Cook NR, Oberman A, et al: Angiotensinogen genotype, sodium reduction, weight loss, and prevention of hypertension: trials of hypertension prevention, phase II. Hypertension 1998; 32: 393-401. – reference: 17. Nakano Y, Oshima T, Watanabe M, Matsuura H, Kajiyama G, Kambe M: Angiotensin I-converting enzyme gene polymorphism and acute response to captopril in essential hypertension. Am J Hypertens 1997; 10: 1064-1068. – reference: 3. Lifton RP, Dluhy RG, Powers M, et al: A chimaeric 11 beta-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension. Nature 1992; 355: 262-265. – reference: 4. Lifton RP: Molecular genetics of human blood pressure variation. Science 1996; 272: 676-680. – reference: 22. Takami S, Katsuya T, Rakugi H, et al: Angiotensin II type 1 receptor gene polymorphism is associated with increase of left ventricular mass but not with hypertension. Am J Hypertens 1998; 11: 316-321. – reference: 23. Katsuya T, Horiuchi M, Minami S, et al: Genomic organization and polymorphism of human angiotensin II type 2 receptor: no evidence for its gene mutation in two families of human premature ovarian failure syndrome. Mol Cell Endocrinol 1997; 127: 221-228. – reference: 10. Katsuya T, Sato N, Asai T, et al: Association of polymorphism in the promoter region of the apolipoprotein E gene with diastolic blood pressure in normotensive Japanese. Hypertens Res 2000; 23: 271-275. – reference: 30. Okamura A, Ohishi M, Rakugi H, et al: Pharmacogenetic analysis of the effect of angiotensin-converting enzyme inhibitor on restenosis after percutaneous transluminal coronary angioplasty. Angiology 1999; 50: 811-822. – reference: 25. Hingorani AD, Jia H, Stevens PA, Hopper R, Dickerson JE, Brown MJ: Renin-angiotensin system gene polymorphisms influence blood pressure and the response to angiotensin converting enzyme inhibition. J Hypertens 1995; 13: 1602-1609. – reference: 6. Chang SS, Grunder S, Hanukoglu A, et al: Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1. Nat Genet 1996; 12: 248-253. – reference: 7. Wang WY, Glenn CL, Zhang W, Benjafield AV, Nyholt DR, Morris BJ: Exclusion of angiotensinogen gene in molecular basis of human hypertension: sib-pair linkage and association analyses in Australian anglo-caucasians. 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SubjectTerms | Antihypertensive Agents - therapeutic use Blood Pressure - drug effects essential hypertension Female gene polymorphism Genetic Variation genetics Genotype Humans Hypertension - drug therapy Hypertension - genetics Hypertension - physiopathology Male pharmacogenetics Polymorphism, Genetic Renin-Angiotensin System - genetics Treatment Outcome |
Title | Effects of Antihypertensive Drugs and Gene Variants in the Renin-Angiotensin System |
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