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

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.

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.

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.

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