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

Abstract

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 -6G3 A, -532C3 T, -20A3 C, and 704T3 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 -20A3 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 (nϭ399, rϭ0.23, PϽ0.0001), but absent in those with at least one copy of the -20C allele (nϭ122, rϭ0.01, Pϭ0.89). The M235T polymorphism did not impact on the BMI-BP relation. Specificity of the -20A3 C 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.

Associations between adiposity, family history of CHD and blood pressure in 3–8 year-old children

“…In contrast, previous work has shown adiposity-family history interactions with regard to diabetes 38 and breast cancer, 39 and another has shown smoking-FHCHD interactions on cardiovascular disease mortality 40 in adults. Currently, there is considerable interest in gene-adiposity interactions on BP [17][18][19] using DNA technologies. These reports have shown that the -20A-C polymorphism in the AGT promotor region, 18 ACE I/D, 19 and Arg16Gly polymorphism of the beta 2 adrenoreceptor 2 interact with various indices of adiposity (BMI and waist-to-hip ratio) and various BP phenotypes (resting and ambulatory BP).…”

“…Currently, there is considerable interest in gene-adiposity interactions on BP [17][18][19] using DNA technologies. These reports have shown that the -20A-C polymorphism in the AGT promotor region, 18 ACE I/D, 19 and Arg16Gly polymorphism of the beta 2 adrenoreceptor 2 interact with various indices of adiposity (BMI and waist-to-hip ratio) and various BP phenotypes (resting and ambulatory BP). In the context of human growth and BP, Lever and Harrap 41 have suggested that a master gene, which they refer to as 'basal growth potential gene', has pleiotropic control over somatic growth, obesity and BP.…”

“…Indeed, recent studies in adults indicate that specific genetic markers modify the relationship between adiposity and BP. [17][18][19] However, genotyping is an expensive laboratory procedure that is not entirely feasible in certain environments. On the other hand, a family medical history questionnaire is inexpensive, feasible, and easy to administer.…”

Genetics of arterial hypertension and hypotension

“…Many additional polymorphisms, however, have been identified in the AGT gene, including an additional promoter polymorphism at −20. This polymorphism is also interesting, since depending on the genotype different response elements are generated, including those for estrogen receptor α, upstream regulatory factor and members of the COUP-TF family, which correlates with different phenotypes, including pregnancydependent variations in AGT levels, non-modulating hypertension and an altered relationship between BMI and blood pressure (Zhao et al 1999;Morgan et al 2000;Hilgers et al 2001;Tiago et al 2002). Current research efforts address the haplotype structure of the AGT gene, which should be comparatively easy given the short length of the gene of only ∼12 kb.…”

Assosiation Analysys of 11 Polymorphisms of SNPS With Endothelium Dependent Vasodilatation in Children With Diabetes Mellitus Type 1

“…Інсерційно-делеційний полімор-фізм 16-го інтрону гена ангіотензинперет-ворювального ферменту (AСЕ) визначали із застосуванням полімеразної ланцюгової реакції (ПЛР) із наступним електрофорезом отриманих ампліфікатів [12]. Для виявлення поліморфізмів наступних генів: G 894 →T -поліморфізм 7-го екзону гена ендотеліальної NO-синтази (eNOS) [13], Arg 60 →His -полі-морфізм гена, що кодує одну з індуцибель-них субодиниць протеасоми (LMP2) [14], Met 235 →Thr -поліморфізм гена ангіотензи-ногена (AGT) [15], A 1166 →C -поліморфізм гена рецептора 1-го типу ангіотензину ІІ (ATR1) [16], C -1562 →T -поліморфізм гена металопротеїнази 9 (MMP9) [17], Т -381 →C -поліморфізм гена натрійуретичного пепти-ду типу В (NPPB) [18] застосовували ПЛР із наступним аналізом довжини рестрикційних фрагментів. C -1306 →T -поліморфізм гена металопротеїнази 2 (MMP2) визначали із застосуванням алель -специфічної ПЛР [19].…”