Department of Nephrology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Pediatr Nephrol. 2013 Mar;28(3):387-99. doi: 10.1007/s00467-012-2206-9. Epub 2012 Jul 5.
Advances in genetic mapping and sequencing techniques have led to substantial progress in the study of rare monogenic (Mendelian) forms of abnormal blood pressure. Many disease-defining pathways for hypertension have been identified in the past two decades. Perturbations in renal salt handling appear to be a common mechanism underlying these rare syndromes of hypertension. Excess activation at various points in the mineralocorticoid signaling pathway and malfunctioning of the autonomic (specifically sympathetic) nervous system have both been implicated in inducing hypertension, while complementary studies examining low blood pressure phenotypes have identified novel pathways exclusively linked to renal salt wasting in either the thick ascending limb or the distal nephron. The genetic defects and the physiological and cellular pathways affected in these various disorders are reviewed here. Importantly, studies have suggested that genetic variation affecting these same genes and pathways may play an important role in explaining the variation of blood pressure levels in the general population. The investigation of rare syndromes of human blood pressure variation has important implications for improving the diagnosis and treatment of hypertension.
遗传图谱和测序技术的进步使得对罕见的单基因（孟德尔）形式的异常血压的研究取得了重大进展。在过去的二十年中，已经确定了许多高血压的疾病定义途径。肾脏盐处理的紊乱似乎是这些罕见高血压综合征的共同机制。在醛固酮信号通路的各个点的过度激活以及自主（特别是交感）神经系统的功能障碍都与诱导高血压有关，而互补的研究检查低血压表型已确定与厚升支或远端肾单位中的肾盐耗竭相关的新途径。在此，回顾了这些不同疾病中涉及的遗传缺陷以及受影响的生理和细胞途径。重要的是，研究表明，影响这些相同基因和途径的遗传变异可能在解释一般人群中血压水平的变异性方面起着重要作用。对人类血压变化的罕见综合征的研究对改善高血压的诊断和治疗具有重要意义。
