Influence of Gender and Genetic Variability on Plasma Angiotensin Peptides

Reyes‐Engel, Armando; Morcillo, Luis; Aranda, Francisco J.; Ruiz, M.; Gaitán, María Jesús; Mayor-Olea, Álvaro; Aranda, Pedro J.; Ferrario, Carlos M.

doi:10.3317/jraas.2006.015

Cited by 45 publications

(32 citation statements)

References 36 publications

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“…Indeed, after the initial observation that the AGT 235T may be associated with higher AGT levels than the AGT 235M allele (63), subsequent studies showed that the AGT M235T polymorphism may account for no more than 5% of AGT variability (67). Moreover, in the only study showing a relationship between the T allele and increased angiotensin II plasma levels, the association could be detected only in male patients (68). This may explain why studies following the original report by Rogus et al (66) failed to detect any significant association between AGT variants and diabetic (69 -71) or nondiabetic (72,73) chronic kidney disease.…”

Section: Other Ras Polymorphisms and Their Interactions With The Ace mentioning

confidence: 77%

Angiotensin Converting Enzyme Insertion/Deletion Polymorphism and Renoprotection in Diabetic and Nondiabetic Nephropathies

Ruggenenti

Bettinaglio

Pinares

et al. 2008

Clinical Journal of the American Society of Nephrology

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Despite the huge amount of studies looking for candidate genes, the ACE gene remains the unique, well-characterized locus clearly associated with pathogenesis and progression of chronic kidney disease, and with response to treatment with drugs that directly interfere with the renin angiotensin system (RAS), such as angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists (ARA). The II genotype is protective against development and progression of type I and type II nephropathy and is associated with a slower progression of nondiabetic proteinuric kidney disease. ACE inhibitors are particularly effective at the stage of normoalbuminuria or microalbuminuria in both type I and type II diabetics with the II genotype, whereas the DD genotype is associated with a better response to ARA therapy in overt nephropathy of type II diabetes and to ACE inhibitors in male patients with nondiabetic proteinuric nephropathies. The role of other RAS or non-RAS polymorphisms and their possible interactions with different ACE I/D genotypes are less clearly defined. Thus, evaluating the ACE I/D polymorphism is a reliable tool to identify patients at risk and those who may benefit the most of renoprotective therapy with ACE inhibitors or ARA. This may guide pharmacologic therapy in individual patients and help design clinical trials in progressive nephropathies. Moreover, it might help optimize prevention and intervention strategies at population levels, in particular, in countries where resources are extremely limited and 1 million patients continue to die every year of cardiovascular or renal disease.

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Section: Other Ras Polymorphisms and Their Interactions With The Ace mentioning

confidence: 77%

Angiotensin Converting Enzyme Insertion/Deletion Polymorphism and Renoprotection in Diabetic and Nondiabetic Nephropathies

Ruggenenti

Bettinaglio

Pinares

et al. 2008

Clinical Journal of the American Society of Nephrology

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“…Peripheral blood Ang-(1–7) levels were significantly higher in men than in women [9]. Deletion of angiotensin receptor type II (AT 2 ) has a sex-dependent effect on cognitive function and ischemic brain damage [40].…”

Section: Discussionmentioning

confidence: 99%

“…Sex differences in blood pressure are also evident in experimental models and human subjects, yet the mechanisms underlying this disparity remain equivocal [4,5,6,7]. The characterization of sex-based differences in experimental models of hypertension has focused on the components of the circulating renin-angiotensin system (RAS) [7,8,9]. The RAS not only plays a critical role in blood pressure control, but is also involved in learning and memory mechanisms [10,11,12].…”

Section: Introductionmentioning

confidence: 99%

Different Isoforms of Nitric Oxide Synthase Are Involved in Angiotensin-(1–7)-Mediated Plasticity Changes in the Amygdala in a Gender-Dependent Manner

Staschewski¹,

Kulisch²,

Albrecht³

2011

Neuroendocrinology

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Background: The amygdala receives afferent sensory input and processes information related to hydromineral balance. Angiotensin acts on and through the amygdala to stimulate thirst and sodium appetite. In addition, different angiotensins seem to play a role in cognition and learning mechanisms by acting on and through the amygdala. Recently, we showed that angiotensin-(1–7) (Ang-(1–7)) enhances the magnitude of long-term potentiation (LTP) in the lateral nucleus of the amygdala (LA) via the Mas receptor. Methods: Extracellular field potentials were measured in the LA. Results: LA-LTP induced by stimulation of the external capsule was nitric oxide (NO)-dependent because the NO synthase (NOS) inhibitor L-NAME reduced LA-LTP. The LA-LTP was also reduced in both male and female nNOS and eNOS knockout mice. In male eNOS^–/– mice, Ang-(1–7) enhanced LA-LTP, whereas the LTP-enhancing effect of Ang-(1–7) was missing in female eNOS^–/– mice. Therefore, the LTP-enhancing effect of Ang-(1–7) was mediated by eNOS in females. In contrast, Ang-(1–7) strongly enhanced the LTP in nNOS^–/– females, whereas the effect of Ang-(1–7) was missing in nNOS^–/– males. Thus, Ang-(1–7) induced an increase in the magnitude of LTP via the involvement of nNOS in males. Conclusion: Our data support not only the hypothesis that NO contributes to plasticity changes in the lateral amygdala, but also show for the first time a gender-dependent involvement of different isoforms of NOS in the mediation of Ang-(1–7) on LTP in the amygdala.

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“…26,27 Few studies demonstrate genderrelated comparisons with genes, regarding multifactorial disorders as stroke, and refer to oestrogen receptor genes. 28,29 Regarding ACE gene, a limited number of studies demonstrate certain differences regarding gender, such as the higher levels of Ang-I and Ang-II in DD females in a series of healthy individuals 22 and the higher levels of renin and prorenin levels in DD women. 24 In this second study, the renin and prorenin levels were higher in males compared with females, independently of genotypes and alleles.…”

Section: Discussionmentioning

confidence: 99%

Gender association of the angiotensin-converting enzyme gene with ischaemic stroke

Markoula

Giannopoulos

Kostoulas

et al. 2011

J Renin Angiotensin Aldosterone Syst

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We examined the association of the NG011648 polymorphism (insertion/deletion) of the angiotensin-converting enzyme (ACE) gene with ischaemic stroke occurrence, subtype of ischaemic stroke and ischaemic stroke patients’ gender. Patients with first ever ischaemic stroke were recruited prospectively in a period of 18 months. Controls were matched with the patients for age, gender, and known risk factors for stroke. Demographic data, medical history, and vascular risk factors were collected. Genotypes were determined by polymerase chain reaction (PCR) and restriction enzyme analysis. Stroke and control groups were compared in regard to the prevalence of the NG011648 polymorphism. One hundred and seventy-six patients with ischaemic stroke and 178 controls were recruited and genotyped for NG011648 polymorphism (I/D) of the ACE gene. No significant difference in allele and genotype distributions emerged between control and patient groups, nor in the two subtype groups of lacunars and large artery atherosclerosis. After the data were stratified by gender, a low incidence of II homozygosity in female patients versus female controls ( p = 0.05) and male patients ( p = 0.013, Z score: -2.49) was found. Our results indicate that I/D polymorphisms may have a role in stroke onset, in respect to gender, with a possible favourable effect of II genotype in females.

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Influence of Gender and Genetic Variability on Plasma Angiotensin Peptides

Cited by 45 publications

References 36 publications

Angiotensin Converting Enzyme Insertion/Deletion Polymorphism and Renoprotection in Diabetic and Nondiabetic Nephropathies

Angiotensin Converting Enzyme Insertion/Deletion Polymorphism and Renoprotection in Diabetic and Nondiabetic Nephropathies

Different Isoforms of Nitric Oxide Synthase Are Involved in Angiotensin-(1–7)-Mediated Plasticity Changes in the Amygdala in a Gender-Dependent Manner

Gender association of the angiotensin-converting enzyme gene with ischaemic stroke

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