Liljedahl Ulrika, Lind Lars, Kurland Lisa, Berglund Lars, Kahan Thomas, Syvänen Ann-Christine
Department of Medical Sciences, Uppsala University, Uppsala University Hospital, Entrance 70, 3rd floor, 751 85 Uppsala, Sweden.
BMC Cardiovasc Disord. 2004 Sep 28;4(1):16. doi: 10.1186/1471-2261-4-16.
Dyslipidemia has been associated with hypertension. The present study explored if polymorphisms in genes encoding proteins in lipid metabolism could be used as predictors for the individual response to antihypertensive treatment.
Ten single nucleotide polymorphisms (SNP) in genes related to lipid metabolism were analysed by a microarray based minisequencing system in DNA samples from ninety-seven hypertensive subjects randomised to treatment with either 150 mg of the angiotensin II type 1 receptor blocker irbesartan or 50 mg of the beta1-adrenergic receptor blocker atenolol for twelve weeks.
The reduction in blood pressure was similar in both treatment groups. The SNP C711T in the apolipoprotein B gene was associated with the blood pressure response to irbesartan with an average reduction of 19 mmHg in the individuals carrying the C-allele, but not to atenolol. The C16730T polymorphism in the low density lipoprotein receptor gene predicted the change in systolic blood pressure in the atenolol group with an average reduction of 14 mmHg in the individuals carrying the C-allele.
Polymorphisms in genes encoding proteins in the lipid metabolism are associated with the response to antihypertensive treatment in a drug specific pattern. These results highlight the potential use of pharmacogenetics as a guide for individualised antihypertensive treatment, and also the role of lipids in blood pressure control.
血脂异常与高血压有关。本研究探讨了脂质代谢相关蛋白编码基因的多态性是否可作为个体对抗高血压治疗反应的预测指标。
采用基于微阵列的微测序系统,对97例高血压患者的DNA样本中的10个脂质代谢相关基因的单核苷酸多态性(SNP)进行分析。这些患者被随机分为两组,一组接受150mg的1型血管紧张素II受体阻滞剂厄贝沙坦治疗,另一组接受50mg的β1肾上腺素能受体阻滞剂阿替洛尔治疗,为期12周。
两个治疗组的血压降低情况相似。载脂蛋白B基因中的SNP C711T与厄贝沙坦的血压反应相关,携带C等位基因的个体平均血压降低19mmHg,但与阿替洛尔无关。低密度脂蛋白受体基因中的C16730T多态性预测了阿替洛尔组收缩压的变化,携带C等位基因的个体平均降低14mmHg。
脂质代谢相关蛋白编码基因的多态性与抗高血压治疗的反应呈药物特异性模式相关。这些结果突出了药物遗传学作为个体化抗高血压治疗指南的潜在用途,以及脂质在血压控制中的作用。