van Wieren-de Wijer Diane B M A, Maitland-van der Zee Anke-Hilse, de Boer Anthonius, Stricker Bruno H Ch, Kroon Abraham A, de Leeuw Peter W, Bozkurt O, Klungel Olaf H
Department of Pharmacoepidemiology & Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences , University of Utrecht, PO Box 80082, 3508 TB Utrecht, The Netherlands.
Pharm World Sci. 2009 Apr;31(2):158-64. doi: 10.1007/s11096-008-9264-x. Epub 2008 Nov 30.
To describe the design, recruitment and baseline characteristics of participants in a community pharmacy based pharmacogenetic study of antihypertensive drug treatment.
Participants enrolled from the population-based Pharmaco-Morbidity Record Linkage System.
We designed a nested case-control study in which we will assess whether specific genetic polymorphisms modify the effect of antihypertensive drugs on the risk of myocardial infarction. In this study, cases (myocardial infarction) and controls were recruited through community pharmacies that participate in PHARMO. The PHARMO database comprises drug dispensing histories of about 2,000,000 subjects from a representative sample of Dutch community pharmacies linked to the national registrations of hospital discharges.
In total we selected 31010 patients (2777 cases and 28233 controls) from the PHARMO database, of whom 15973 (1871 cases, 14102 controls) were approached through their community pharmacy. Overall response rate was 36.3% (n = 5791, 794 cases, 4997 controls), whereas 32.1% (n = 5126, 701 cases, 4425 controls) gave informed consent to genotype their DNA. As expected, several cardiovascular risk factors such as smoking, body mass index, hypercholesterolemia, and diabetes mellitus were more common in cases than in controls.
Furthermore, cases more often used beta-blockers and calcium-antagonists, whereas controls more often used thiazide diuretics, ACE-inhibitors, and angiotensin-II receptor blockers. We have demonstrated that it is feasible to select patients from a coded database for a pharmacogenetic study and to approach them through community pharmacies, achieving reasonable response rates and without violating privacy rules.
描述一项基于社区药房的抗高血压药物治疗药物遗传学研究中参与者的设计、招募情况及基线特征。
参与者来自基于人群的药物发病率记录链接系统。
我们设计了一项巢式病例对照研究,以评估特定基因多态性是否会改变抗高血压药物对心肌梗死风险的影响。在本研究中,病例(心肌梗死患者)和对照通过参与PHARMO的社区药房招募。PHARMO数据库包含来自荷兰社区药房代表性样本中约200万名受试者的药物配药历史记录,并与国家医院出院登记系统相链接。
我们从PHARMO数据库中总共选取了31010名患者(2777例病例和28233名对照),其中15973名(1871例病例,14102名对照)通过其社区药房联系。总体响应率为36.3%(n = 5791,794例病例,4997名对照),而32.1%(n = 5126,701例病例,4425名对照)给予知情同意对其DNA进行基因分型。正如预期的那样,吸烟、体重指数、高胆固醇血症和糖尿病等几种心血管危险因素在病例中比在对照中更常见。
此外,病例更常使用β受体阻滞剂和钙拮抗剂,而对照更常使用噻嗪类利尿剂、ACE抑制剂和血管紧张素II受体阻滞剂。我们已经证明,从编码数据库中选择患者进行药物遗传学研究并通过社区药房联系他们是可行的,能够获得合理的响应率且不违反隐私规则。