Published Online
on August 26, 2002

A more recent version of this article appeared on September 17, 2002

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Submitted on May 6, 2002
Revised on June 24, 2002
Accepted on June 25, 2002

Angiotensinogen Gene Promoter Region Variant Modifies Body Size-Ambulatory Blood Pressure Relations in Hypertension

Armindo D. Tiago MD, Nilesh J. Samani MD, Geoffrey P. Candy PhD, Richard Brooksbank MS, Elena N. Libhaber MS, Pinhas Sareli MD, Angela J. Woodiwiss PhD^*, and Gavin R. Norton MD, PhD

From the Cardiovascular Genomics Research Unit, Departments of Physiology and Medicine (A.D.T., G.P.C., R.B., A.J.W., G.R.N.), Cardiology (G.P.C., E.N.L., P.S.), and Nuclear Cardiology (G.P.C.), Johannesburg and Chris Hani-Baragwanath Hospitals and the University of the Witwatersrand, South Africa, and the Division of Cardiology (N.J.S.), Department of Medicine, University of Leicester, United Kingdom.

^* To whom correspondence should be addressed. E-mail: woodiwissaj{at}physiology.wits.ac.za.

Background—The extent to which genes modify the relationship between risk factors for hypertension and blood pressure (BP) is unclear. As angiotensinogen is expressed in adipose tissue and angiotensinogen (AGT) gene promoter variants influence the production of angiotensinogen, we evaluated the role of AGT gene variants as potential modifiers of body size-BP relations.

Methods and Results—Five hundred twenty-one hypertensives of African origin sampled from a group with a high mean body mass index (BMI) had 24-hour ambulatory BP (ABP) measurements determined off therapy and were genotyped for the AGT -6GA, -532CT, -20AC, and 704TC (M235T) gene variants. Genotypes were also determined in 547 control subjects of African origin who had a normal clinic BP. The -6A and -532C alleles were concordant with the M235T variant. Although AGT gene variants had no independent effects on either the presence of hypertension or ABP values in hypertensives, the -20AC polymorphism had a marked influence on the relation between ambulatory systolic BP and BMI. This relation was present in patients homozygous for the -20A allele (n=399, r=0.23, P<0.0001), but absent in those with at least one copy of the -20C allele (n=122, r=0.01, P=0.89). The M235T polymorphism did not impact on the BMI-BP relation. Specificity of the -20AC polymorphism effect on the BMI-BP relation is further indicated by the lack of effect on the systolic BP-age relation.

Conclusion—An AGT gene promoter region variant is an important modifier of the relation between body size and BP. Hence, these data corroborate the notion that genetic modifiers can produce a profound impact on BP-phenotypic relations.

Key words: genetics • hypertension • obesity

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