難治性高血壓-基因與遺傳背景(存儲版)
【正文】 。 hom., homozygous 家族性與散發(fā)原醛的遺傳機制 三種臨床類型： ? FH1: GRA，嵌合基因突變（ CYP11B2/B1) ? FH2: 最常見的兩側(cè)腎上腺增生（ BAH， bilateral adrenal hyperplasia), 致病基因突變尚未找到， 連鎖位點 7p22； ? FH3: KCNJ5 突變引起產(chǎn)生醛固酮的腺瘤（ APAs aldosterone producing adenomas)。螺內(nèi)酯治療會加重高血壓。 高血壓 復(fù)雜原因 在難治性高血壓當中，繼發(fā)性高血壓 比我們想象的 多； 單基因高血壓是繼發(fā)性高血壓重要病因之一 ? 三級甲等 醫(yī)院 4429例難治性高血壓中 %為繼發(fā)性高血壓 ， 60歲以上的難治性高血壓患者中 17%為繼發(fā)性高血壓 （ Anderson GH Jr, etal. J Hypertens 1994。 ）青年難治性高血壓住院（ 20202020年）患者病因分析 青年頑固性高血壓有 40%能找到原因，解除病因，免得終生服藥。 hypotension or hypertension ? PHAI itself has been recognized as a heterogeneous syndrome that includes at least 2 clinically distinguishable entities with either renal or multiple target an defects (MTOD). ? Early childhood hyperkalemia, or renal tubular acidosis (RTA) type IV subtype 5, is a variant of the renal form of PHAI. microRNAs as new partners for WNK1 expression influenced by Na+, K+ regimen ? two kidneyspecific microRNAS, miR192 and miR215, that target sequence in the 3’UTR of the gene. In vitro assays showed that miR192, but not miR215, is able to regulate WNK1 expression at the posttranscriptional level only. ? miR192 expression is strongly inhibited by Na+ depletion, K+ loading and aldosterone infusion. In addition, LWNK1 expression, while unaffected by any of the conditions at the RNA level, was increased at the posttranscriptional level by aldosterone and confirmed that KSWNK1 transcripts level was increased by K+ loading and aldosterone. ? Taken together, these results suggest that downregulation of miR192 could be involved in the stimulation of WNK1 expression by aldosterone in the kidney. ? A new working hypothesis under which microRNAs could play a role in the regulation of ion transport in the kidney (ElviraMatelot et Am Soc Nephrol. 2020). 擬鹽皮質(zhì)激素增多癥（ AME） 本病為常染色體隱性遺傳疾病。 家族與散發(fā)原發(fā)性醛固酮增多癥遺傳機制 FH:家族性高醛固酮血癥 Circ Res 2020。 Gordon’s 綜合征 ? 高血鉀、高血 Cl代酸發(fā)生在高血壓之前，直到成年方出現(xiàn)高血壓。 ? 鹽皮質(zhì)類固醇受體激活型突變， Na重吸收增加 。 ? 治療：糖皮質(zhì)激素，螺內(nèi)酯或伊普利酮， 小劑量地塞米松 – mg qd 或 強的松（ prednisolone） – 5 mg qd 足夠。 ? 禁忌：鹽皮質(zhì)類固醇受體拮抗劑（螺內(nèi)酯，依普利酮） Glucocorticoidremediable aldosteronism [(GRA) familia
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