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 inHypertension Research Vol. 24; no. 4; pp. 463 - 467
Main Authors OGIHARA, Toshio, MOTONE, Motoharu, FUKUDA, Masayuki, KATSUYA, Tomohiro, ASAI, Takashi, RAKUGI, Hiromi, FU, Yuxiao, OHISHI, Mitsuru, IWASHIMA, Yoshio, SUGIMOTO, Ken, HATANAKA, Yasuko, HIGAKI, Jitsuo
Format Journal Article
LanguageEnglish
Published England The Japanese Society of Hypertension 2001
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Online AccessGet full text
ISSN0916-9636
1348-4214
1348-4214
DOI10.1291/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)
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.
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Snippet Many genes and environmental factors are involved in the pathogenesis of hypertension, but the exact cause of essential hypertension has not yet been...
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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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