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The Journal of Clinical Endocrinology & Metabolism Vol. 89, No. 5 2301-2305
Copyright © 2004 by The Endocrine Society

Polymorphisms of the Renin-Angiotensin System Influence Height in Normotensive Women in a Spanish Population

F. J. Chaves, D. Corella, J. V. Sorli, P. Marin-Garcia, M. Guillen and J. Redon

Unidad Mixta de Investigación (F.J.C.), Hospital Clínico Universitario de Valencia, 46010 Valencia, Spain; Genetic and Molecular Epidemiology Unit (D.C., J.V.S., M.G.), Department of Preventive Medicine, School of Medicine, University of Valencia, 46010 Valencia, Spain; European Bioinformatic Institute (P.M.-G.), The European Molecular Biology Laboratory Outstation, Hinxton, Cambridge CB10 1SD, United Kingdom; and Servicio de Medicina Interna (J.R.), Hospital Clínico Universitario de Valencia, University of Valencia, 46010 Valencia, Spain

Address all correspondence and requests for reprints to: F. J. Chaves, Unidad Mixta de Investigación, Hospital Clínico Universitario de Valencia, Avda., Blasco Ibañez N° 17, 46010 Valencia, Spain. E-mail: felipe.chaves{at}uv.es.


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Discussion
 References
 
The objective of this study was to analyze the influence of the polymorphisms G-6A of the angiotensinogen gene, insertion/deletion (I/D) of the angiotensin-converting enzyme, and C573T of the angiotensin II AT1 receptor gene on a healthy, middle-age population. A total of 370 (194 women) healthy normotensive Caucasian subjects, aged 25–50 yr old, were selected from the general population. A significant association was found between height and the C573T polymorphism in women (P < 0.001). After adjustment for age, this association remained significant (P < 0.002). Thus, the lowest height values were from subjects carrying TT genotype (CC, 1.627 ± 0.008 m; CT, 1.595 ± 0.006 m; TT, 1.586 ± 0.010 m; P = 0.002). Likewise, the I/D polymorphism was associated with height (P = 0.002) in women. It remained significant after adjustment for age and the lowest height for the DD genotype (II, 1.629 ± 0.011 m; ID, 1.603 ± 0.006 m; DD, 1.591 ± 0.007 m; P = 0.016). For both C573T and I/D polymorphisms, there was an allele dosage effect. Moreover, an additive and independent effect of the C573T polymorphism (P = 0.006) and the I/D polymorphism (P = 0.045) on height was observed. In contrast, no association with height was observed for the G-6A polymorphism. In conclusion, additive effects between polymorphisms of the renin-angiotensin system genes and height were observed in healthy women. These results should be studied by other groups in other populations and ethnic groups. Whether or not these associations need to be considered in the epidemiological studies analyzing the relationship between polymorphisms of the renin-angiotensin system genes and such height-influenced parameters as blood pressure merits further study.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Discussion
 References
 
HUMAN HEIGHT IS a multifactorial trait that results from the interaction of genetic and environmental factors. Heritability of final height seems to be higher than 80% in developed countries where standard living conditions minimize the effect of undernutrition (1). Mutations of a small number of genes strongly influence height, resulting in short stature (2, 3, 4), such as mutations in GH system or short stature homeobox gene. Moreover, several chromosome regions (5, 6, 7) and some polymorphisms in candidate genes (8, 9, 10) have been linked to height, although their impact is minimal. Because most of the genetic variation in height remains unknown, it is interesting to look for it in other potential candidate systems to understand this complex trait.

The renin-angiotensin system (RAS) plays a key role in fetal growth, organ development, and cellular differentiation and proliferation (11, 12, 13, 14, 15, 16). It has been shown in rats that inhibition of AT1 receptors impairs somatic and renal growth (17) and double knockout for Agtr1a and Agtr1b genes causes a generalized impairment of growth (18). Polymorphisms of the genes codifying for the RAS components, angiotensinogen (AGT) (19, 20), angiotensin-converting enzyme (ACE) (21), and an association with angiotensin II (AngII) activity in AngII AT1 receptor (AGTR1) (22), have been associated with AGT gene expression, levels of ACE protein, or activity of AngII, respectively.

The putative involvement of RAS in processes that could affect human development and final stature has encouraged us to study their possible relationships. In the present study, we analyzed the influence of polymorphism G-6A of the AGT gene, polymorphism insertion/deletion (I/D) of the ACE gene, and polymorphism C573T of the AGTR1 gene on height in a middle-age, healthy population.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Discussion
 References
 
A total of 370 healthy normotensive subjects (176 men and 194 women) from Valencia (Spain), ages 25–50 yr and all Caucasian, were studied. These individuals were randomly selected from the general population as healthy control subjects matched by age and gender for one case-control study with hypertensive patients (23). The study was approved by the Committee for the Protection of Human Subjects of the Sagunto Hospital and the Ethic Committee of University Clinic Hospital of Valencia. All participants gave informed written consent to participate in this protocol.

Anthropometric measurements were taken for all subjects using standard techniques; weight with light clothing was measured using digital scales, and height without shoes was measured with a fixed stadiometer. Blood pressure was measured with a calibrated mercury sphygmomanometer following British Hypertension Society Standards.

Genomic DNA was obtained from peripheral blood by standard methods. Polymorphism analyses were carried out by PCR amplification of the region containing each of the polymorphisms. In the case of I/D polymorphism of the ACE gene, PCR product was analyzed by agarose electrophoresis (24). The C573T polymorphism of AGTR1 gene was detected by PCR product digestion with FokI and single strand confirmational polymorphism (SSCP) analysis (25). The G-6A polymorphism of the AGT was detected by SSCP analysis (26). Those individuals in whom an abnormal SSCP band was detected were discarded. In all cases, informed consent for the genetic study was required. Polymorphism assessment was performed in duplicate and analyzed by two different people to avoid any mistake in the interpretation of the SSCP or agarose gel bands. The error rate was lower than 1% in all cases.

Statistical analysis

Allele frequencies were estimated by gene counting. The {chi}2 test was used to compare categorical variables and to test differences between observed and expected frequencies, assuming Hardy-Weinberg equilibrium. Normal distribution for continuous variables was checked. The ANOVA procedure was used to compare mean differences for continuous variables among genotypes or among ethnic groups. Once differences existing among means were established, the Bonferroni test was applied to determine which means differ, with correction for multiple comparisons. In addition, P values for linear trends between categories were also calculated in the ANOVA analysis. The influence of covariates (such as age) in the comparison of means was controlled by multiple linear regression analysis. This analysis, with dummy variables for categorical and interaction terms, was also used to test independence and interaction between genotypes. All P values were two-sided, and 95% confidence intervals were calculated.


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Discussion
 References
 
The demographic, anthropometric, and clinical characteristics of the study population grouped by gender are shown in Table 1Go. Height was significantly higher in men than in women. The distribution of genotypes and alleles of the polymorphisms analyzed were similar for both men and women, and they were in Hardy-Weinberg equilibrium. Considering the differences in height between men and women, we stratified the analysis of their association with the polymorphisms by gender. A statistically significant association was found between the C573T polymorphism of the AGTR1 gene in women (P < 0.001) but not in men. In addition, a linear trend of the allele effects was found in women (P for trend = 0.001). The lowest height values were for those subjects carrying the TT genotype (CC, 1.628 ± 0.058 m; CT, 1.595 ± 0.064 m; TT, 1.586 ± 0.058 m; P = 0.001). After applying Bonferroni correction for multiple comparisons, differences among the genotypes were maintained (CC vs. CT, P = 0.009; CC vs. TT, P = 0.007), and no significant differences were found between the CT and TT genotypes. Likewise, the I/D polymorphism of the ACE gene was associated with height (P = 0.002) in the women with the lowest height for the DD genotype (II, 1.631 ± 0.063 m; ID, 1.604 ± 0.060 m; DD, 1.588 ± 0.0632 m; P = 0.002). There were significant differences between the two homozygote genotypes (II vs. DD, P = 0.005). For both C573T and I/D polymorphisms, there was an allele dosage effect (P for trend <= 0.002). To avoid the potential confounding effect of age, these analyses were adjusted for age. After this adjustment, the C573T and I/D polymorphisms remained statistically significant in women (Table 2Go) but not for AGT polymorphism. The association between these polymorphisms and height remained statistically significant after additional adjustment for weight. In contrast, no association with height was observed for the G-6A polymorphism of the AGT gene (Table 2Go).


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  		TABLE 1. Age, anthropometric, and blood pressure characteristics of the study population grouped by gender

 

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  		TABLE 2. Analysis of polymorphisms located in ACE, AGTR1, and AGT in relation to stature in women

 
Considering the associations found between the C573T and the I/D polymorphisms and height in women, the joint effect of these polymorphisms on this trait was further tested taking into consideration the additional adjustment by age. First, we tested the statistical significance of the interaction term between these genetic variants, and no statistically significant modification of the effect was found. Conversely, an additive and independent effect of the C573T polymorphism (P = 0.006) and the I/D polymorphism (P = 0.045) on height was observed (Fig. 1Go). Women sharing the TT and DD genotypes were the shortest, and women sharing the CC and II genotypes were the tallest, with a 7-cm difference between them.



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  		FIG. 1. Representation of height for women distributed by I/D and AGTR1 polymorphisms. Additive and independent effect is shown.

 

   Discussion
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
References
 
In the present study, the C573T polymorphism of AGTR1 and the I/D polymorphism of ACE are statistically associated with the final height of healthy, middle-age, normotensive Caucasian women but not men. However, because a statically significant association found in a study does not mean direct causality, our results should be interpreted taking into account this potential limitation. Moreover, in women, these genetic variants showed a clear gene-dosage, independent, and additive effect on height. This additive effect has been observed in the statistical regression model, and it should be further confirmed by haplotype analysis.

In most of the previous works in which RAS polymorphisms have been analyzed, the stature has not been studied. In many cases, only body mass index as unique anthropometric data has been included. Stature and RAS polymorphisms have been analyzed only in two works (27, 28). The results of Turner et al. (28) show a similar tendency as ours, but without statistical significance, in the group of 5–30 yr olds but not in the other groups. One limitation of these results may be that they have analyzed all women, independently of blood pressure. Therefore, the purpose of these studies and the populations analyzed do not allow for direct comparison to our results.

In our study, the analyzed population allowed minimizing bias for the purpose of the study. Thus, the age range is such that all individuals had completed their development and had not started significant stature shortening due to aging. The selection of only normotensive subjects tried to minimize the known interaction between short stature and hypertension due to an inverse relationship between height and blood pressure values (29, 30) and avoid the inclusion of individuals whose RAS system expression could be altered, as is the case in hypertensives (31, 32, 33, 34). The Hardy-Weinberg equilibrium was fulfilled for the polymorphisms analyzed, and the genotype distribution was similar to other Spanish populations of the same age and sex (35).

The association observed between height and polymorphisms of ACE and AGTR1 can be explained through the impact of the activity of AngII in tissues during growth or an unknown association with other potential genes in linkage disequilibrium. Finally, we do not completely exclude the possibility that the result may be a false positive in terms of causality due to statistical fluctuation, population stratification, or other factors. However, in our study, population stratification can be discarded because no ethnic groups were included. Type I errors, which are an important cause of false-positive results, have been minimized by the Bonferroni correction and by the magnitude of the obtained P values. However, we have demonstrated a statistically significant allelic trend, supporting causality by following the dose-response criteria.

The observed data indicated the possibility that AngII activity may influence growth as has been indicated in previous data about inhibition of ACE and double knockout for AGTR1 (AGTR1A and AGTR1B) in rats (17, 18). Recently, it has been shown in humans that appropriate AGTR1 activity in the placenta is important for correct human fetal growth (12), and this has been related to final height (36). The presence of the D allele of the I/D polymorphism of ACE has been associated with higher levels of circulating ACE (29, 37, 38), higher ACE expression (21, 39), and different cell and tissue growth response (40, 41). The higher level of ACE could lead to an increase in AngII generation, but it is unknown how this or other polymorphisms of this gene modify the activity of local RAS genes and the final activity. There is no information about the functional impact of the C573T polymorphism of AGTR1.

The differential impact in women and men was noteworthy. Dynamic interactions among sex steroidal hormones and other hormonal systems have a major role in the achievement of full height potential by regulating linear bone growth (42). The pubertal increase in growth velocity associated with GH has been traditionally attributed to testicular androgen secretion in boys and to estrogens or adrenal androgen secretion in girls. Research data, however, has indicated that estrogen may be the principal hormone stimulating the pubertal growth spurt in boys as well as girls, but prepubertal estradiol concentrations are significantly higher in girls than in boys (43). Estrogens modify gene expression of the RAS components, decreasing ACE levels, reducing the number of AGTR1, and increasing the AGT levels. In the presence of higher levels of estrogens, the impact of the different genotypes on ACE and/or AGTR1 expression can be uncovered. Thus, the influence of polymorphisms of ACE and/or AGTR1 genes on growth may be observed in conditions with higher levels of estrogens. In this way, RAS gene expression is regulated by estrogens (44, 45, 46).

The absence of association between height and the polymorphism G-6A of AGT do not disagree with the hypothesis that that overactivity of AngII could influence height. Although G-6A is a functional polymorphism, presence of the A allele results in an increase of AGT synthesis. The production of AngII depends on renin and ACE, which can modulate the synthesis independent of AGT production, and the importance of this polymorphism in different cells, tissues, or development stages could vary. Furthermore, AngII activity depends on the number and activity of AGTR1. Thus, an increase in AGT levels does not necessarily result in RAS activation. Likewise, high estrogen levels increase AGT levels (43), decreasing the possibility of detecting differences in activity among the G-6A polymorphism genotypes.

From all this data, it could be thought that small modifications of RAS activity could have an influence on human development and final height. The polymorphisms studied in AGTR1 and ACE could be associated with modifications in this activity, and in normotensive women, they could affect their final stature in our population. However, the influence of these polymorphisms studied on stature could be different in other populations due to different genetic and environmental factors. Therefore, these results should be considered cautiously, and this putative influence should be analyzed by other investigators in other samples, including populations from other regions of Spain.

In conclusion, additive effects between polymorphisms of the RAS genes and height were observed in healthy women. Whether or not this possible association needs to be considered in the epidemiological studies analyzing the relationship between polymorphisms of the RAS genes and parameters influenced by height, like blood pressure, merits further study.


   Footnotes
 
This work was supported by Grants FIS 018/98, 01/0069-01, and 01/3047, RCMN C03/08, and FIS2002-PI021096 of the Fondo de Investigaciones Sanitarias of the Spanish Health Ministry.

Abbreviations: ACE, Angiotensin-converting enzyme; AGT, angiotensinogen; AGTR1, angiotensin II AT1 receptor; AngII, angiotensin II; I/D, insertion/deletion; RAS, renin-angiotensin system; SSCP, single strand confirmational polymorphism.

Received June 19, 2003.

Accepted February 1, 2004.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
 References
 

  1. Silventoinen K, Kaprio J, Lahelma E, Koskenvuo M 2000 Relative effect of genetic and environmental factors on body height: differences across birth cohorts among Finnish men and women. Am J Public Health 90:627–630[Abstract/Free Full Text]
  2. Procter AM, Phillips III JA, Cooper DN 1998 The molecular genetics of growth hormone deficiency. Hum Genet 103:255–272[CrossRef][Medline]
  3. Rosenfeld RG, Rosenbloom AL, Guevara-Aguirre J 1994 Growth hormone (GH) insensitivity due to primary GH receptor deficiency. Endocr Rev 15:369–390[Abstract/Free Full Text]
  4. Rao E, Weiss B, Fukami M, Rump A, Niesler B, Mertz A, Muroya K, Binder G, Kirsch S, Winkelmann M, Nordsiek G, Heinrich U, Breuning MH, Ranke MB, Rosenthal A, Ogata T, Rappold GA 1997 Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome. Nat Genet 16:54–63[CrossRef][Medline]
  5. Hirschhorn JN, Lindgren CM, Daly MJ, Kirby A, Schaffner SF, Burtt NP, Altshuler D, Parker A, Rioux JD, Platko J, Gaudet D, Hudson TJ, Groop LC, Lander ES 2001 Genomewide linkage analysis of stature in multiple populations reveals several regions with evidence of linkage to adult height. Am J Hum Genet 69:106–116[CrossRef][Medline]
  6. Perola M, Ohman M, Hiekkalinna T, Leppavuori J, Pajukanta P, Wessman M, Koskenvuo M, Palotie A, Lange K, Kaprio J, Peltonen L 2001 Quantitative-trait-locus analysis of body-mass index and of stature, by combined analysis of genome scans of five Finnish study groups. Am J Hum Genet 69:117–123[CrossRef][Medline]
  7. Wiltshire S, Frayling TM, Hattersley AT, Hitman GA, Walker M, Levy JC, O’Rahilly S, Groves CJ, Menzel S, Cardon LR, McCarthy MI 2002 Evidence for linkage of stature to chromosome 3p26 in a large U.K. family data set ascertained for type 2 diabetes. Am J Hum Genet 70:543–546[CrossRef][Medline]
  8. Lehrer S, Rabin J, Stone J, Berkowitz GS 1994 Association of an estrogen receptor variant with increased height in women. Horm Metab Res 26:486–488[Medline]
  9. Hasegawa Y, Fujii K, Yamada M, Igarashi Y, Tachibana K, Tanaka T, Onigata K, Nishi Y, Kato S, Hasegawa T 2000 Identification of novel human GH-1 gene polymorphisms that are associated with growth hormone secretion and height. J Clin Endocrinol Metab 85:1290–1295[Abstract/Free Full Text]
  10. Lorentzon M, Lorentzon R, Nordstrom P 2000 Vitamin D receptor gene polymorphism is associated with birth height, growth to adolescence, and adult stature in healthy caucasian men: a cross-sectional and longitudinal study. J Clin Endocrinol Metab 85:1666–1670[Abstract/Free Full Text]
  11. Buttar HS 1997 An overview of the influence of ACE inhibitors on fetal-placental circulation and perinatal development. Mol Cell Biochem 176:61–71[CrossRef][Medline]
  12. Laskowska M, Leszczynska-Gorzelak B, Oleszczuk J 2003 Placental angiotensin II receptor AT1R in normotensive patients and its correlation between infant birth weight. Eur J Obstet Gynecol Reprod Biol 109:166–170[CrossRef][Medline]
  13. Gomez RA, Norwood VF 1995 Developmental consequences of the renin-angiotensin system. Am J Kidney Dis 26:409–431[Medline]
  14. Hohenfellner K, Fogo A, Kon V 1999 Renin-angiotensin genes in renal development and the occurrence and progression of renal diseases. Semin Nephrol 19:148–154[Medline]
  15. Leung PS, Chappell MC 2003 A local pancreatic renin-angiotensin system: endocrine and exocrine roles. Int J Biochem Cell Biol 35:838–846[CrossRef][Medline]
  16. Engeli S, Schling P, Gorzelniak K, Boschmann M, Janke J, Ailhaud G, Teboul M, Massiera F, Sharma AM 2003 The adipose-tissue renin-angiotensin-aldosterone system: role in the metabolic syndrome? Int J Biochem Cell Biol 35:807–825[CrossRef][Medline]
  17. Tufro-McReddie A, Romano LM, Harris JM, Ferder L, Gomez RA 1995 Angiotensin II regulates nephrogenesis and renal vascular development. Am J Physiol 269:F110–F115
  18. Oliverio MI, Kim HS, Ito M, Le T, Audoly L, Best CF, Hiller S, Kluckman K, Maeda N, Smithies O, Coffman TM 1998 Reduced growth, abnormal kidney structure, and type 2 (AT2) angiotensin receptor-mediated blood pressure regulation in mice lacking both AT1A and AT1B receptors for angiotensin II. Proc Natl Acad Sci USA 95:15496–15501[Abstract/Free Full Text]
  19. Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F 1990 An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 86:1343–1346
  20. Inoue I, Nakajima T, Williams CS, Quackenbush J, Puryear R, Powers M, Cheng T, Ludwig EH, Sharma AM, Hata A, Jeunemaitre X, Lalouel JM 1997 A nucleotide substitution in the promoter of human angiotensinogen is associated with essential hypertension and affects basal transcription in vitro. J Clin Invest 99:1786–1797[Medline]
  21. Costerousse O, Allegrini J, Lopez M, Alhenc-Gelas F 1993 Angiotensin I-converting enzyme in human circulating mononuclear cells: genetic polymorphism of expression in T-lymphocytes. Biochem J 290:33–40
  22. Miller JA, Thai K, Scholey JW 1999 Angiotensin II type 1 receptor gene polymorphism predicts response to losartan and angiotensin II. Kidney Int 56:2173–2180[CrossRef][Medline]
  23. Giner V, Corella D, Chaves FJ, Pascual JM, Portoles O, Marin P, Lozano JV, Armengod ME, Redon J 2001 Renin-angiotensin system genetic polymorphisms and essential hypertension in the Spanish population. Med Clin (Barc) 117:525–529[Medline]
  24. Redon J, Chaves FJ, Liao Y, Pascual JM, Rovira E, Armengod ME, Cooper RS 2000 Influence of the I/D polymorphism of the angiotensin-converting enzyme gene on the outcome of microalbuminuria in essential hypertension. Hypertension 35:490–495[Abstract/Free Full Text]
  25. Chaves FJ, Pascual JM, Rovira E, Armengod ME, Redon J 2001 Angiotensin II AT1 receptor gene polymorphism and microalbuminuria in essential hypertension. Am J Hypertens 14:364–370[CrossRef][Medline]
  26. Chaves FJ, Giner V, Corella D, Pascual JM, Marin P, Armengod ME, Redon J 2002 Body weight changes and the A-6G polymorphism of the angiotensinogen gene. Int J Obes Relat Metab Disord 26:1–6[CrossRef][Medline]
  27. Hernandez D, de la Rosa A, Barragan A, Barrios Y, Salido E, Torres A, Martin B, Laynez I, Duque A, De Vera A, Lorenzo V, Gonzalez A 2003 The ACE/DD genotype is associated with the extent of exercise-induced left ventricular growth in endurance athletes. J Am Coll Cardiol 42:527–532[Abstract/Free Full Text]
  28. Turner ST, Boerwinkle E, Sing CF 1999 Context-dependent associations of the ACE I/D polymorphism with blood pressure. Hypertension 34:773–778[Abstract/Free Full Text]
  29. Sichieri R, Siqueira KS, Pereira RA, Ascherio A 2000 Short stature and hypertension in the city of Rio de Janeiro, Brazil. Public Health Nutr 3:77–82[Medline]
  30. Voors AW, Harsha DW, Webber LS, Berenson GS 1982 Relation of blood pressure to stature in healthy young adults. Am J Epidemiol 115:833–840[Free Full Text]
  31. Johren O, Golsch C, Dendorfer A, Qadri F, Hauser W, Dominiak P 2003 Differential expression of AT1 receptors in the pituitary and adrenal gland of SHR and WKY. Hypertension 41:984–990[Abstract/Free Full Text]
  32. Naito Y, Tsujino T, Fujioka Y, Ohyanagi M, Iwasaki T 2002 Augmented diurnal variations of the cardiac renin-angiotensin system in hypertensive rats. Hypertension 40:827–833[Abstract/Free Full Text]
  33. Faloia E, Gatti C, Camilloni MA, Mariniello B, Sardu C, Garrapa GG, Mantero F, Giacchetti G 2002 Comparison of circulating and local adipose tissue renin-angiotensin system in normotensive and hypertensive obese subjects. J Endocrinol Invest 25:309–314[Medline]
  34. Tamura K, Chiba E, Yokoyama N, Sumida Y, Yabana M, Tamura N, Takasaki I, Takagi N, Ishii M, Horiuchi M, Umemura S 1999 Renin-angiotensin system and fibronectin gene expression in Dahl Iwai salt-sensitive and salt-resistant rats. J Hypertens 17:81–89[Medline]
  35. Poch E, La Sierra Ad A, Gonzalez-Nunez D, Oriola J, Redon J, Chaves FJ, Marin P, Giner V, Pamies E, Villar J, Ramirez R, Stiefel P, Rodriguez Perez JC, Rodriguez Esparragon F, Martinez E, Carrion L, Sanchis C, Divison JA 2002 Genetic polymorphisms of the renin-angiotensin system and essential hypertension. Med Clin (Barc) 118:575–579[Medline]
  36. Heinrich UE 1992 Intrauterine growth retardation and familial short stature. Baillieres Clin Endocrinol Metab 6:589–601[CrossRef][Medline]
  37. Tiret L, Rigat B, Visvikis S, Breda C, Corvol P, Cambien F, Soubrier F 1992 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 51:197–205[Medline]
  38. Winkelmann BR, Nauck M, Klein B, Russ AP, Bohm BO, Siekmeier R, Ihnken K, Verho M, Gross W, Marz W 1996 Deletion polymorphism of the angiotensin I-converting enzyme gene is associated with increased plasma angiotensin-converting enzyme activity but not with increased risk for myocardial infarction and coronary artery disease. Ann Intern Med 125:19–25[Abstract/Free Full Text]
  39. Danser AH, Schalekamp MA, Bax WA, van den Brink AM, Saxena PR, Riegger GA, Schunkert H 1995 Angiotensin-converting enzyme in the human heart. Effect of the deletion/insertion polymorphism. Circulation 92:1387–1388[Abstract/Free Full Text]
  40. Itoh H, Mukoyama M, Pratt RE, Gibbons GH, Dzau VJ 1993 Multiple autocrine growth factors modulate vascular smooth muscle cell growth response to angiotensin II. J Clin Invest 91:2268–2274
  41. Ribichini F, Steffenino G, Dellavalle A, Matullo G, Colajanni E, Camilla T, Vado A, Benetton G, Uslenghi E, Piazza A 1998 Plasma activity and insertion/deletion polymorphism of angiotensin I-converting enzyme: a major risk factor and a marker of risk for coronary stent restenosis. Circulation 97:147–154[Abstract/Free Full Text]
  42. Mauras N 2001 Growth hormone and sex steroids. Interactions in puberty. Endocrinol Metab Clin North Am 30:529–544[CrossRef][Medline]
  43. Juul A 2001 The effects of oestrogens on linear bone growth. Hum Reprod Update 7:303–313[Abstract/Free Full Text]
  44. Gordon MS, Chin WW, Shupnik MA 1992 Regulation of angiotensinogen gene expression by estrogen. J Hypertens 10:361–366[CrossRef][Medline]
  45. Gallagher PE, Li P, Lenhart JR, Chappell MC, Brosnihan KB 1999 Estrogen regulation of angiotensin-converting enzyme mRNA. Hypertension 33:323–328[Abstract/Free Full Text]
  46. Garcia MJ, Martinez-Martos JM, Mayas MD, Carrera MP, Ramirez-Exposito MJ 2003 Hormonal status modifies renin-angiotensin system-regulating aminopeptidases and vasopressin-degrading activity in the hypothalamus-pituitary-adrenal axis of male mice. Life Sci 73:525–538[CrossRef][Medline]



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