Li Yanna, Jain Sudhir, Patil Sai, Kumar Ashok
Department of Pathology, New York Medical College, Valhalla, NY 10595, United States.
Vascul Pharmacol. 2006 Jan;44(1):29-33. doi: 10.1016/j.vph.2005.09.009. Epub 2005 Nov 21.
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.
肥胖与高血压及其他心血管疾病相关，尤其在非裔美国人中。人血管紧张素原（AGT）基因在其启动子的1.2 kb区域有7个单核苷酸多态性（SNP）。最近的研究表明，-217A变体与非裔美国人和中国人的高血压相关。hAGT基因的核苷酸序列显示，-217A变体几乎总是与-532T、-793A和-1074T变体一起出现（形成单倍型AAT），而-217G变体几乎总是与-532C、-793G和-1074G变体一起出现（形成单倍型GGG）。由于hAGT基因在脂肪组织中表达，其在该组织中的表达可能在高血压中起作用，我们分析了单倍型AAT和GGG对该基因在脂肪细胞中表达的作用。我们在此表明，与含有GCGG单倍型的报告构建体相比，含有hAGT基因单倍型AAT的报告构建体在原代脂肪细胞和分化脂肪细胞中瞬时转染时具有增强的启动子活性。在肝脏和脂肪细胞中含有单倍型AAT的AGT基因表达增加可能是高血压的一个促成因素。
