難治性高血壓-基因與遺傳背景(完整版)
【正文】 yperaldosteronism type II (FH II) ? similar to GRA (FH I) in that excess mineralocorticoid production is responsible for the development of hypertension, but the hypertension is not suppressible by dexamethasone. ? Autosomal dominant inheritance suggests that FH II is due to a single gene mutation and, although the gene has not been identified, the locus has recently been narrowed to a band on chromosome 7 ? Many patients with FH II have a family history of adrenal hyperplasia or adenoma, which suggests that a growth factor may be involved. ? Widened criteria for screening have revealed FH II to be more mon than previously believed, and it may be the most mon inherited type of hypertension in adults. However, although reninaldosterone abnormalities have been reported in affected adolescents, hypertension due to FH II typically does not manifest until adulthood. ? FH II is clinically and biochemically indistinguishable from noninherited primary aldosteronism, and currently, the diagnosis can be only confirmed by positive family history until geic detection is available. Congenital adrenal hyperplasia ? Defects in 11hydroxylase and 17hydroxylase result in overproduction of 21hydroxylated steroids, which activate 。 ? 治療：限制鹽攝入，噻嗪利尿劑， ENaC 拮抗劑（阿米洛利，三甲阿番） 。與 IV 腎小管酸中毒不同： Gordon腎功多正常；常伴高血鈣 。 and ? 類鹽皮質(zhì)類固醇增多癥 （ AMEapparent mineralocorticoid excess)：調(diào)節(jié)糖皮質(zhì)類固醇 11HD2 滅活突變（ glucocorticoidmetabolizing 11βhydroxysteroid dehydrogenase type 2 enzyme ). Liddle 氏綜合征： 最常見的單基因高血壓 診斷： 周圍血基因組 DNA， 治療： 低鈉飲食， ENaC抑制劑（阿米洛利或三甲阿番 ） 鹽皮質(zhì)類固醇受體拮抗劑無效 遠(yuǎn)曲小管（ DCT） 主要的 apical Na 轉(zhuǎn)運體 是噻嗪敏感的 NaCl交換體 (NCC) 及 集合管主細(xì)胞（ PC） 阿米洛利 –敏感的上 皮鈉通道 epithelial sodium channel (ENaC) K 分泌： 通過尖膜腎髓外鉀通道 renal outer medulla K channel (ROMK) 分泌鉀 WNK4 phosphorylates NCC, which prevents incorporation of the transporter into the apical membrane. WNK4 exerts a tonic baseline suppression on NCC activity, which explains why interference with WNK4 can lead to augmented Na transport. Gordon’s 綜合征 (家族性高血鉀高血壓 , 假性低醛固酮血癥 II型 ) ? Gordon’s 表型特征：常染色體顯性遺傳，高血鉀 , 輕度代謝性酸中毒 , 高血壓，對小劑量噻嗪敏感。HSD11BⅡ 基因突變不僅導(dǎo)致基因表達(dá)降低或?qū)Φ孜锏挠H和力降低，也可導(dǎo)致 11βHSDⅡ 蛋白酶的穩(wěn)定性降低，半衰期顯著縮短。 而生理狀態(tài)下的
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