The G-217A variant of the angiotensinogen gene affects basal transcription and is associated with hypertension in a Taiwanese population.
OBJECTIVE
Polymorphisms of the angiotensinogen (AGT) gene, especially in the promoter region, are in linkage concordance and are associated with hypertension. In this study, we examined the role of AGT promoter polymorphisms, including G-217A, A-6G and M235T variants, and their promoter function in essential hypertension in Taiwanese populations.


METHODS
An association study was conducted to assess the genotype distribution between hypertensive patients and normotensive subjects. We also used a transient transfection assay to examine basal transcriptional activity of G-217A and A-6G variants in a mammalian cell system.


METHODS
Hypertensive subjects (390) and normotensive controls (388) of Taiwanese ethnicity were genotyped for the AGT G-217A, A-6G and M235T variants. Promoter activity was studied by cloning the promoter region (-614 to +41 bp) of AGT into the pSEAP2-Basic reporter vector and performing a transient transfection assay in HuH7 and HepG2 cells.


RESULTS
The G-217A variant of the AGT gene was significantly associated with hypertension (P = 0.0047), but the A-6G and M235T polymorphisms were not (P = 0.17 and P = 0.33, respectively). Furthermore, the recessive model of homozygous genotype (-217AA) conferred a high risk for hypertension (odds ratio 3.64) in this population. The -217A variant expressed higher transcriptional activity than -217G in vitro.


CONCLUSIONS
Our study showed a significant association between the -217A variant of the AGT gene and hypertension. This variant plays a functional role in basal transcription of AGT, and may confer a risk for hypertension in Taiwanese populations.
Department of Physiology, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan, ROC.
Shyh-Jong
SJ
Wu
Fu-Tien
FT
Chiang
Jun-Ran
JR
Jiang
Kwan-Lih
KL
Hsu
Tser-Haw
TH
Chern
Yung-Zu
YZ
Tseng
D000225:Adenine; D000808:Angiotensinogen / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D014644:Genetic Variation; D006147:Guanine; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D013624:Taiwan; D014158:Transcription, Genetic
D000808:Angiotensinogen; D006147:Guanine; D000225:Adenine