A haplotype of the angiotensinogen gene is associated with hypertension in African Americans
A haplotype of the angiotensinogen gene is associated with hypertension in African Americans
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DOI：
10.1111/j.1440-1681.2005.04217.x
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发表时间：
2005-05-01
影响因子：
2.9
通讯作者：
Jain, S
中科院分区：
文献类型：
--
作者：
Kumar, A;Li, Y;Jain, S
1.高血压是心肌梗塞、心力衰竭、血管疾病、中风和肾衰竭的严重危险因素。成年白人中高血压的发病率为25-30%，非裔美国人中高血压引起的并发症甚至更高。2．肾素-血管紧张素系统在血压调节中发挥着重要作用，之前的研究表明血管紧张素原（AGT）基因位点与人类原发性高血压有关。早期研究表明，第 235 位氨基酸将甲硫氨酸转化为苏氨酸的单核苷酸多态性 (SNP) 与白种人人群的高血压有关。然而，该SNP与非裔美国人和中国人群的高血压无关。3．我们发现人类AGT基因启动子-217位点存在A/G多态性，并表明非裔美国高血压患者基因组DNA中-217位等位基因A的频率显着增加。4．我们还表明： (i) 含有核苷 A 在 -217 的 AGT 基因启动子的报告构建体在瞬时转染时具有增加的启动子活性； (ii) 当核苷 A 存在于 -217 时，转录因子的 CCAAT 盒增强子结合蛋白 (C/EBP) 家族和糖皮质激素受体 (GR) 优先结合启动子的该区域。此外，变体-217A始终与变体-532T、-793A和-1074T一起存在于人AGT基因启动子中。5．这些数据表明，含有-217A、-532T、-793A和-1074T的AGT单倍型可能参与该基因转录的增加，并可能在人类高血压中发挥作用。
1. Hypertension is a serious risk factor for myocardial infarction, heart failure, vascular disease, stroke and renal failure. The incidence of hypertension is 25-30% in the adult Caucasian population and complications due to hypertension are even greater in African Americans.2. The renin-angiotensin system plays an important role in the regulation of blood pressure and previous studies have suggested that angiotensinogen (AGT) gene locus is linked with human essential hypertension. Earlier studies suggested that a single nucleotide polymorphism (SNP) that converts methionine to threonine at amino acid 235 is associated with hypertension in the Caucasian population. However, this SNP is not associated with hypertension in African American and Chinese populations.3. We have found an A/G polymorphism at -217 of the human AGT gene promoter and have shown that the frequency of allele A at -217 is significantly increased in the genomic DNA of African American hypertensive patients.4. We have also shown that: (i) reporter constructs containing the AGT gene promoter with nucleoside A at -217 have increased promoter activity on transient transfection; and (ii) the CCAAT box enhancer binding protein (C/EBP) family of transcription factors and glucocorticoid receptor (GR) bind preferentially to this region of the promoter when nucleoside A is present at -217. In addition, variant -217A is always present with variants -532T, -793A and -1074T in the human AGT gene promoter.5. These data suggest that the AGT haplotype containing -217A, -532T, -793A and -1074T may be involved in increased transcription of this gene and may play a role in human hypertension.