Angiotensinogen promoter variants influence gene expression in human kidney and visceral adipose tissue.
Human angiotensinogen (AGT) gene promoter polymorphisms (G-217A; A-20C; G-6A) influence AGT transcription in vitro and have been implicated in the genetics of essential hypertension. We analysed the association among AGT promoter variants and AGT mRNA levels in human kidney and visceral adipose tissue (VAT) in vivo. Samples of kidney and VAT were obtained from 35 consecutive patients undergoing renal surgery. The AGT gene promoter of each patient was sequenced to identify variants. AGT gene expression was studied by real-time PCR TaqMan assay. Clinical data obtained before surgery were also considered in the statistical analysis. Two new polymorphisms at -175 and at -163 were identified. Although AGT expression was significantly higher in VAT than in the kidney, when both variants were present together AGT expression in VAT was about fivefold lower (P=0.033) than in the wild haplotype. This lower AGT expression in VAT suggests that the proximity and linkage of -175A and -163A variants might destabilize the binding of specific transcription factors to an acute-phase responsive element 3. Among the known AGT promoter variants, only -20C SNP has an important effect on tissue-specific differential AGT expression in the human tissues studied, inducing a 3.8-fold increase in AGT mRNA localized only in the kidney medulla (P=0.038). The other known polymorphisms (G-6A; G-217A) were not associated with different levels of AGT expression. Our results support the hypothesis that some human AGT promoter variants influence transcriptional activity in a tissue-specific way in humans.
Sarzani
R
R
Department of Internal Medicine and Cardiovascular Disease, University of Ancona Politecnica delle Marche, Ancona, Italy. r.sarzani@univpm.it
Bordicchia
M
M
Marcucci
P
P
Minardi
D
D
Muzzonigro
G
G
Dessì-Fulgheri
P
P
Rappelli
A
A
D000368:Aged; D000808:Angiotensinogen / Q000235:genetics*; D001483:Base Sequence; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D006977:Hypertension, Renal / Q000235:genetics*; D050152:Intra-Abdominal Fat / Q000502:physiology*; D007672:Kidney Cortex / Q000502:physiology*; D007679:Kidney Medulla / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009765:Obesity / Q000235:genetics; D009928:Organ Specificity; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism
D012333:RNA, Messenger; D000808:Angiotensinogen