A haplotype of angiotensinogen gene that is associated with essential hypertension increases its promoter activity in adipocytes.
Obesity is associated with hypertension and other cardiovascular diseases especially in the African-American population. Human angiotensinogen (AGT) gene has seven single nucleotide polymorphisms (SNPs) in 1.2 kb region of its promoter. Recent studies have shown that variant -217A is associated with hypertension in African-American and Chinese population. Nucleotide sequence of the hAGT gene has shown that variant -217A almost always occurs with variants -532T, -793A and -1074T (forming haplotype AAT) and variant -217G almost always occurs with variants -532C, -793G and -1074G (forming haplotype GGG). Since hAGT gene is expressed in the adipose tissue and its expression in this tissue may play a role in hypertension, we have analyzed the role of haplotypes AAT and GGG on the expression of this gene in adipocytes. We show here that a reporter construct with haplotype AAT of the hAGT gene has increased promoter activity on transient transfection in pre-adipocytes and differentiated adipocytes as compared to the reporter construct containing GCGG haplotype. Increased expression of the AGT gene containing haplotype AAT in the liver and adipocytes may be a contributing factor for hypertension.
Li
Yanna
Y
Department of Pathology, New York Medical College, Valhalla, NY 10595, United States.
Jain
Sudhir
S
Patil
Sai
S
Kumar
Ashok
A
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000808:Angiotensinogen / Q000235:genetics*; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D051379:Mice; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014158:Transcription, Genetic; D014162:Transfection
D011993:Recombinant Fusion Proteins; D000808:Angiotensinogen; D003907:Dexamethasone