Schuster H, Wienker T E, Bähring S, Bilginturan N, Toka H R, Neitzel H, Jeschke E, Toka O, Gilbert D, Lowe A, Ott J, Haller H, Luft F C
The Clinical Research Unit, Max Delbrück Center for Molecular Medicine, Franz Volhard Clinic, Rudolf Virchow University Hospitals, Humboldt University, Berlin, Germany.
Nat Genet. 1996 May;13(1):98-100. doi: 10.1038/ng0596-98.
Finding genes that cause human hypertension is not straightforward, since the determinants of blood pressure in primary hypertension are multifactorial. One approach to identifying relevant genes is to elucidate rare forms of monogenic hypertension. A relevant mutation may provide a rational starting point from which to analyse the pathophysiology of a condition affecting 20% of the world's population. In 1973 a family with autosomal dominantly inherited brachydactyly and severe hypertension, where the two traits cosegregated completely, was described. We have now re-examined this kindred, and localized the hypertension and brachydactyly locus to chromosome 12p in a region defined by markers D12S364 and D12S87. As the renin-angiotensin-system and sympathetic nervous system respond normally in this form of hypertension, the condition resembles essential hypertension. This feature distinguishes this form of hypertension from glucocorticoid remediable aldosteronism and Liddle's syndrome, which are salt-sensitive forms of monogenic hypertension with very low plasma renin activity. We suggest that identification of the gene involved in hypertension and brachydactyly and its mutation will be of great relevance in elucidating new mechanisms leading to blood pressure elevation.
寻找导致人类高血压的基因并非易事，因为原发性高血压的血压决定因素是多因素的。一种识别相关基因的方法是阐明单基因高血压的罕见形式。一个相关的突变可能提供一个合理的起点，由此来分析影响世界20%人口的一种疾病的病理生理学。1973年描述了一个常染色体显性遗传短指症和严重高血压的家族，其中这两种性状完全共分离。我们现在重新研究了这个家族，并将高血压和短指症基因座定位到12号染色体短臂上由标记D12S364和D12S87界定的一个区域。由于肾素-血管紧张素系统和交感神经系统在这种高血压形式中反应正常，这种病症类似于原发性高血压。这一特征将这种高血压形式与糖皮质激素可治性醛固酮增多症和利德尔综合征区分开来，后两者是血浆肾素活性非常低的盐敏感性单基因高血压形式。我们认为，识别与高血压和短指症相关的基因及其突变对于阐明导致血压升高的新机制将具有重大意义。
