Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension is a serious health problem particularly for African-Americans. Previous studies have suggested that angiotensinogen (AGT) gene locus is involved in human essential hypertension. We have recently shown that an A/G polymorphism at -217 in the promoter of the AGT gene is associated with essential hypertension especially in African-Americans. We report here that A/G polymorphism at -217 affects the glucocorticoid-induced promoter activity of the human AGT gene. We show that recombinant glucocorticoid receptor (GR) binds strongly to the AGT gene promoter when nucleoside A is present at -217, and dexamethasone treatment increases the interleukin 6 induced promoter activity of reporter constructs containing nucleoside A at -217. Similarly cotransfection of GR and C/EBP beta or C/EBP delta increases the promoter activity of reporter construct containing nucleoside A at -217. Since AGT is an acute phase protein, we propose that increased expression of -217A allele of the AGT gene by glucocorticoids and C/EBP family of transcription factors may be involved in essential hypertension.
 ...
PMID:A single-nucleotide polymorphism in human angiotensinogen gene is associated with essential hypertension and affects glucocorticoid induced promoter activity. 1563 May 92

Insulin-like growth factor 1 (IGF1) exerts important endocrine and paracrine functions in the cardiovascular system. We identified the common variant -1411C>T in the IGF1 upstream promoter P1, located within several overlapping transcription factor binding sites. Using transient transfection assays, we identified this site as a functional enhancer. The T allele-carrying enhancer, compared with the C allelic portion, exerts significantly reduced or even abrogated activity, respectively, in SaOs-2 and HepG2 (all P<0.0001) as well as in differentiated THP-1 macrophages. Electrophoretic mobility shift assay and subsequent supershift experiments in HepG2 identified c-Jun as the binding partner exclusively to the T allele, whereas CCAAT/enhancer-binding protein delta and interferon consensus site-binding protein/interferon-regulating factor 8 interacted only with the C allelic promoter portion. Furthermore, genotyping in a case-control study for essential hypertension (n=745 hypertensive patients; n=769 normotensive control subjects) for this variant revealed an odds ratio for hypertension of 0.73 (95% confidence interval 0.58-0.91, P=0.006) associated with the T allele, and normotensive subjects carrying the protective T allele displayed a significant decrease in diastolic (P=0.036) and systolic (P=0.024) blood pressure levels. We here report detection of a functional enhancer module in the upstream IGF1 promoter region, which might play a key role in local IGF1 bioavailability. Whether -1411C>T is also associated with other IGF1-related disease phenotypes should be evaluated further in population studies.
 ...
PMID:Molecular genetic analysis of a human insulin-like growth factor 1 promoter P1 variation. 1910 45