Angiotensinogen gene promoter region variant modifies body size-ambulatory blood pressure relations in hypertension.
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.


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 -6G-->A, -532C-->T, -20A-->C, and 704T-->C (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 -20A-->C 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 -20A-->C polymorphism effect on the BMI-BP relation is further indicated by the lack of effect on the systolic BP-age relation.


CONCLUSIONS
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.
Tiago
Armindo D
AD
Cardiovascular Genomics Research Unit, Department of Physiology, Johannesburg and Chris Hani-Baragwanath Hospitals and the University of the Witwatersrand, South Africa.
Samani
Nilesh J
NJ
Candy
Geoffrey P
GP
Brooksbank
Richard
R
Libhaber
Elena N
EN
Sareli
Pinhas
P
Woodiwiss
Angela J
AJ
Norton
Gavin R
GR
D000808:Angiotensinogen / Q000235:genetics*; D018660:Blood Pressure Monitoring, Ambulatory; D001824:Body Constitution; D015992:Body Mass Index; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications; D010641:Phenotype; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012307:Risk Factors
D000808:Angiotensinogen