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Influence of Gender and Genetic Variability on Plasma Angiotensin Peptides

Department of Biochemistry and Molecular Biology Faculty of Medicine. University of Málaga, Spain, engel{at}uma.es

Luis Morcillo

Department of Biochemistry and Molecular Biology Faculty of Medicine. University of Málaga, Spain

Francisco Javier Aranda

Department of Nephrology and Hypertension Unit. Carlos Haya Hospital, Malaga, Spain

Maximiliano Ruiz

Department of Biochemistry and Molecular Biology Faculty of Medicine. University of Málaga, Spain

Maria Jesús Gaitan

Department of Biochemistry and Molecular Biology Faculty of Medicine. University of Málaga, Spain

Álvaro Mayor-Olea

Department of Biochemistry and Molecular Biology Faculty of Medicine. University of Málaga, Spain

Pedro Aranda

Department of Nephrology and Hypertension Unit. Carlos Haya Hospital, Malaga, Spain

Carlos Maria Ferrario

Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA

Introduction. We analysed the influence of three polymorphisms of the renin-angiotensin system (RAS) (I/D from angiotensin-converting enzyme [ACE], M235T from angiotensinogen gene [ATG] and A1166C from AT₁ receptors) on plasma levels of angiotensin I (Ang I), angiotensin II (Ang II) and angiotensin-(1-7) [Ang-(1-7)].

Materials and Methods. The study population consisted of a homogeneous group of 93 healthy subjects (43 men and 50 women, mean age: 20.67±2.75 years). The mean blood pressure (BP) was 126±7/76±5 (SD) mmHg and the mean body mass index (SD) mmHg and the mean body mass ' (BMI) was 22.4±2.5 kg/m². Angiotensin peptides were separated by high performance liquid chromatography (HPLC) and quantified by radio immuno assay (RIA). Genotypes were determined by polymerase chain reaction (PCR) and restriction enzyme analysis.

Results. Mean peptide levels were 92.48±102.12 pg/ml for Ang I, 22.35±10 pg/ml for Ang II, and 31.65±27.46 pg/ml for Ang-(1-7). Men had significantly higher levels of Ang-(1-7) (37.76±36.47 pg/ml) than women (26.04±13.98 pg/ml) (p<0.05). Among genotypes of each polymorphism, men with the T allele showed higher Ang-(1-7) levels compared with those with the MM genotype (p<0.05). Genotype analysis in women showed that higher Ang I levels were related with the DD genotype. When both genders were compared according to genotype, higher values of Ang-(1-7) levels and its molar ratios were found in men, and there was significantly greater Ang I levels in DD genotypes in women than men (136.72±112.43 vs. 65.36±46.83 pg/mL).

Conclusions. Significant correlations were found between Ang I and Ang II as well as between Ang II and Ang-(1-7) in the different study group distributions. No correlation was found between levels of Ang I and Ang-(1- 7). Certain genotypes exert an influence on angiotensin peptide plasma levels which can only be seen when the population is divided according to gender.

Key Words: Human Angiotensin I • Angiotensin II and Angiotensin-(1-7) peptide levels • I/D angiotensin-converting enzyme • A1166C AT1-receptor • M235T angiotensinogen • Polymorphism

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Journal of Renin-Angiotensin-Aldosterone System, Vol. 7, No. 2, 92-97 (2006)
DOI: 10.3317/jraas.2006.015


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