HAPLOTYPE ANALYSIS OF CYP11B2
HAPLOTYPE ANALYSIS OF CYP11B2
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DOI：
10.3109/07435809509030459
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发表时间：
1995-01-01
影响因子：
2.1
通讯作者：
SLUTSKER, L
中科院分区：
文献类型：
--
作者：
WHITE, PC;SLUTSKER, L
影响醛固酮合成或其调控的多态性可能对血压有影响。例如，人类高血压的常染色体显性形式，糖皮质激素抑制性高醛固酮增多症，是由醛固酮合成酶（CYP11B2）和类固醇-羟化酶（CYP11B1）基因之间的重组引起的，产生了一个嵌合基因，其中CYP11B1启动子和CYP11B2特异性编码序列并在一起。因此，醛固酮的合成受到不适当的调节。我们已经开始对人类CYP11B2和CYP11B1基因进行分析，看看是否存在频繁的多态性，以及它们是否与血压差异有关。我们发现CYP11B2基因有频繁的多态性。启动子中的一个影响转录调节蛋白SF-1的结合。另一种是内含子2中的基因转换，使得大部分内含子具有与CYP11B1相对应的序列。这些多态性处于连锁不平衡状态，定义了3个单倍型。黑人和白人在这些单倍型发生的频率上有显著差异（p < 0.001）。我们需要进一步的研究来确定黑人和白人在血压和醛固酮水平上的差异是否可以部分地用这些CYP11B2等位基因的差异或这些单倍型上连锁不平衡的其他多态性来解释。
Polymorphisms affecting the synthesis of aldosterone or its regulation may have effects on blood pressure. For example, an autosomal dominant form of human hypertension, glucocorticoid suppressible hyperaldosteronism, is caused by recombination between the genes for aldosterone synthase (CYP11B2) and steroid 11 beta-hydroxylase (CYP11B1), creating a chimeric gene in which the CYP11B1 promoter and CYP11B2-specific coding sequences are juxtaposed. Thus, aldosterone synthesis is improperly regulated. We have begun an analysis of the human CYP11B2 and CYP11B1 genes to see if frequent polymorphisms exist and if they are correlated with differences in blood pressure. We have found frequent polymorphisms in CYP11B2. One in the promoter influences binding of the transcriptional regulatory protein, SF-1. Another is a gene conversion in intron 2 so that most of the intron has a sequence corresponding to CYP11B1. These polymorphisms are in linkage disequilibrium, defining 3 haplotypes. Blacks and whites differ significantly (p < 0.001) in the frequency with which these haplotypes occur. Further studies are required to determine if the observed differences between blacks and whites in blood pressure and in aldosterone levels can be explained in part by these allelic differences in CYP11B2 or by other polymorphisms in linkage disequilibrium on these haplotypes.