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Pharmacogenetic Analysis of Captopril Effects on Blood Pressure: Possible Role of the Ednrb (Endothelin Receptor Type B) Candidate Gene

机译:卡托普利对血压影响的药物遗传学分析:Ednrb(B型内皮素受体)候选基因的可能作用

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摘要

The objective of the current study was to search for genetic determinants associated with antihypertensive effects of angiotensin-converting enzyme (ACE) inhibitor captopril. Linkage and correlation analyses of captopril-induced effects on blood pressure (BP) with renal transcriptome were performed in the BXH/HXB recombinant inbred (RI) strains derived from spontaneously hypertensive rat (SHR) and Brown Norway (BN-Lx) progenitors. Variability of blood pressure lowering effects of captopril among RI strains was continuous suggesting a polygenic mode of inheritance. Linkage analysis of captoprilinduced BP effects revealed a significant quantitative trait locus (QTL) on chromosome 15. This QTL colocalized with cis regulated expression QTL (eQTL) for the Ednrb (endothelin receptor type B) gene in the kidney (SHR allele was associated with increased renal expression) and renal expression of Ednrb correlated with captopril-induced BP effects. These results suggest that blood pressure lowering effects of ACE inhibitor captopril may be modulated by the variants at the Ednrb locus.
机译:当前研究的目的是寻找与血管紧张素转换酶(ACE)抑制剂卡托普利的降压作用有关的遗传决定因素。卡托普利诱导的对血压(BP)的影响与肾脏转录组之间的关联和相关性分析是在自发性高血压大鼠(SHR)和布朗挪威(BN-Lx)祖细胞衍生的BXH / HXB重组自交系(RI)中进行的。卡托普利在RI菌株中降血压作用的变化持续不断,这表明遗传是多基因的。卡托普利诱发的BP效应的连锁分析揭示了15号染色体上的重要定量性状基因座(QTL)。该QTL与顺式调节表达QTL(eQTL)在肾脏中的Ednrb(B型内皮素受体)基因共定位(SHR等位基因与肾表达)和Ednrb的肾表达与卡托普利诱导的BP效应相关。这些结果表明,ACE抑制剂卡托普利的降血压作用可以通过Ednrb基因座处的变体来调节。

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