哮喘联盟

   摘要
   临床观察表明使用血管紧张素转换酶抑制剂的中国人咳嗽发生率远高于其他种族。 咳嗽是依那普利最常见的副反应。我们研究了SLCO1B1基因遗传多态性（之前报道该多态性是依那普利药代动力学个体间变异性的重要决定因素）是否与依那普利引起的咳嗽相关。一项服用10mg马来酸依那普利的原发性高血压患者的队列研究中，对450例患者进行基因分型，甄别功能性SLCO1B1基因变体388A > G (Asn130Asp, rs2306283)和 521T > C (Val174Ala, rs4149056)。主要终点结局是咳嗽，当服用依那普利治疗期间参与者出现不明原因的咳嗽或呼吸系统症状时予以记录。SLCO1B1 521C 等位基因带来2倍的依那普利咳嗽相对风险(95%置信区间 [CI] = 1.34-3.04, P = 6.2 × 10(-4))，单体型分析表明SLCO1B1*15/*15携带者咳嗽的相对风险为6.94倍 (95% CI = 1.30-37.07, P = 0.020)。并且，大量证据表明以上现象具有基因剂量效应(携带0、1或2个521C等位基因者咳嗽的百分比：28.2%、42.5%和71.4%, 趋势 P = 6.6 × 10(-4))。我们的研究第一次突出了SLCO1B1 变体是与依那普利咳嗽强相关的。这项发现在为依那普利治疗中提供药物遗传学标记是很有意义的。

 

（苏欣 审校）
Sci Rep. 2015 Nov 26;5:17253. doi: 10.1038/srep17253.


 

SLCO1B1 Variants and Angiotensin Converting Enzyme Inhibitor (Enalapril) -Induced Cough: a Pharmacogenetic Study.
 

Luo JQ1,2,3, He FZ1,2,3, Wang ZM1,2,3, Sun NL4, Wang LY4, Tang GF5, Liu MZ1,2,3, Li Q1,2,3, Chen XP1,2,3, Liu ZQ1,2,3, Zhou HH1,2,3, Zhang W1,2,3.

 

Abstract
Clinical observations suggest that incidence of cough in Chinese taking angiotensin converting enzyme inhibitors is much higher than other racial groups. Cough is the most common adverse reaction of enalapril. We investigate whether SLCO1B1 genetic polymorphisms, previously reported to be important determinants of inter-individual variability in enalapril pharmacokinetics, are associated with the enalapril-induced cough. A cohort of 450 patients with essential hypertension taking 10 mg enalapril maleate were genotyped for the functional SLCO1B1 variants, 388A > G (Asn130Asp, rs2306283) and 521T > C (Val174Ala, rs4149056). The primary endpoint was cough, which was recorded when participants were bothered by cough and respiratory symptoms during enalapril treatment without an identifiable cause. SLCO1B1 521C allele conferred a 2-fold relative risk of enalapril-induced cough (95% confidence interval [CI] = 1.34-3.04, P = 6.2 × 10(-4)), and haplotype analysis suggested the relative risk of cough was 6.94-fold (95% CI = 1.30-37.07, P = 0.020) in SLCO1B1*15/*15 carriers. Furthermore, there was strong evidence for a gene-dose effect (percent with cough in those with 0, 1, or 2 copy of the 521C allele: 28.2%, 42.5%, and 71.4%, trend P = 6.6 × 10(-4)). Our study highlights, for the first time, SLCO1B1 variants are strongly associated with an increased risk of enalapril-induced cough. The findings will be useful to provide pharmacogenetic markers for enalapril treatment.
 

Sci Rep. 2015 Nov 26;5:17253. doi: 10.1038/srep17253.