Interaction Between NOS3 and HMOX1 on Antihypertensive Drug Responsiveness in Preeclampsia

Abstract Objective We examined the interaction of polymorphisms in the genes heme oxygenase- 1 (HMOX1) and nitric oxide synthase (NOS3) in patients with preeclampsia (PE) as well as the responsiveness to methyldopa and to total antihypertensive therapy. Methods The genes HMOX1 (rs2071746, A/T) and NOS3 (rs1799983, G/T) were genotyped using TaqMan allele discrimination assays (Applied Biosystems, Foster City, CA, USA ), and the levels of enzyme heme oxygenase-1 (HO-1) were measured using enzyme-linked immunosorbent assay (ELISA). Results We found interactions between genotypes of the HMOX-1 and NOS3 genes and responsiveness tomethyldopa and that PE genotyped as AT presents lower levels of protein HO-1 compared with AA. Conclusion We found interactions between the HMOX-1 and NOS3 genes and responsiveness to methyldopa and that the HMOX1 polymorphism affects the levels of enzyme HO-1 in responsiveness to methyldopa and to total antihypertensive therapy. These data suggest impact of the combination of these two polymorphisms on antihypertensive responsiveness in PE.

目的 本研究旨在探讨子痫前期（preeclampsia, PE）患者体内血红素氧合酶-1（heme oxygenase-1, HMOX1）与一氧化氮合酶（nitric oxide synthase, NOS3）的基因多态性之间的交互作用，及其对甲基多巴与整体降压治疗的响应性。
方法 采用TaqMan等位基因分型检测技术（美国应用生物系统公司，美国加利福尼亚州福斯特城）对HMOX1基因（rs2071746，A/T位点）与NOS3基因（rs1799983，G/T位点）进行基因分型，并通过酶联免疫吸附试验（enzyme-linked immunosorbent assay, ELISA）检测血红素氧合酶-1（HO-1）的蛋白水平。
结果 本研究发现HMOX1与NOS3基因的基因型与甲基多巴治疗响应性存在交互作用；且基因型为AT的PE患者，其HO-1蛋白水平低于AA基因型患者。
结论 本研究证实HMOX1与NOS3基因的基因型与甲基多巴治疗响应性存在交互作用，且HMOX1基因多态性可在甲基多巴及整体降压治疗的响应过程中影响HO-1酶的蛋白水平。上述数据表明，这两种基因多态性的联合作用可对子痫前期患者的降压治疗响应性产生影响。