G protein β3 gene
G protein β3 gene
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DOI：
10.1161/01.hyp.36.1.33
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发表时间：
2000-07-01
期刊：
影响因子：
8.3
通讯作者：
Siffert, W
中科院分区：
文献类型：
--
作者：
Rosskopf, D;Busch, S;Siffert, W
最近的研究表明，编码G蛋白β 3亚基（GNB 3）的基因中的多态性（C825 T）与高血压和肥胖相关。我们表征了整个GNB 3基因，其跨度为7.5 kb，由11个内含子和10个内含子组成。其启动子缺乏TATA盒，但含有富含GC的区域。GNB 3启动子的功能活性用报告基因测定法进行了验证，该测定法也证明了其可被佛波醇酯诱导。在非洲人、中国人和德国人中，启动子区A（-350）G的一种新的多态性频率（G等位基因）分别为76%、97%和61%。具有A或G等位基因的报告基因构建体在报告蛋白的诱导方面没有差异。编码区（A657 T）发生沉默核苷酸交换，T等位基因频率范围为0.5%至2.4%。另一种多态性（G814 A）导致272位的甘氨酸被丝氨酸取代。在德国人中，A等位基因的频率为10%。最后，在GNB 3的3'非翻译区的C1429 T多态性被确定，在非洲人、中国人和德国人中T等位基因频率分别为38%、17%和30%。单倍型预测表明，在德国GNB 3 825 T与1429 T几乎完全关联，反之亦然。在非人灵长类动物中对这些多态性位点的分析显示，祖先GNB 3基因具有（-350）G、825 C和1429 C等位基因。这是人类GNB 3基因及其启动子区域的首次完整表征，这将使GNB 3在高血压和肥胖症中的流行病学和生物化学研究得以完善。
Recent studies have shown that a polymorphism (C825T) in the gene encoding the G protein beta 3 subunit (GNB3) is associated with hypertension and obesity. We characterized the entire GNB3 gene, which spans 7.5 kb and is composed of 11 introns and 10 introns. Its promoter lacks a TATA box but harbors GC-rich regions. The functional activity of the GNB3 promoter was verified with reporter gene assays that also demonstrated its inducibility by phorbol esters. A novel polymorphism in the promoter region A(-350)G occurred with frequencies (G allele) of 76%, 97%, and 61% in Africans, Chinese, and Germans, respectively. Reporter gene constructs with either the A or the G allele did not differ with regard to inducement of the reporter protein. A silent nucleotide exchange in the coding region (A657T) occurred with T allele frequencies ranging from 0.5% to 2.4%. Another polymorphism (G814A) results in the replacement of glycine by serine at position 272. In Germans, the A allele occurred at a frequency of 10%. Finally, a C1429T polymorphism in the 3' untranslated region of GNB3 was identified that occurred at T allele frequencies of 38%, 17%, and 30% in Africans, Chinese, and Germans, respectively. Haplotype prediction indicated in Germans an almost complete association of GNB3 825T with 1429T, and vice versa. An analysis of these polymorphic loci in nonhuman primates revealed that the ancestral GNB3 gene harbored the (-350)G, 825C, and 1429C alleles. This is the first complete characterization of the human GNB3 gene and its promoter region, which will enable refined epidemiological and biochemical investigations of GNB3 in hypertension and obesity.