Sr Kalpana, G Bharath, Jain Simran, Moorthy Nagaraja, Manjunath Satvic C, Christopher Rita
Sri Jayadeva Institute of Cardiovascular Sciences & Research, Depatmment of Pathology.
Sri Jayadeva Institute of Cardiovascular Sciences & Research, Department of Cardiology, Bannerghatta Road, 9th block Jayanagar, Bangalore - 69, India.
Medicine (Baltimore). 2019 Feb;98(6):e14365. doi: 10.1097/MD.0000000000014365.
Prosthetic Valve Thrombosis (PVT), in spite of the advances in the valve design and the material used, remains a serious complication of mechanical cardiac valve replacement. The factors influencing the development of PVT are: thrombogenicity of the valve, hemodynamics of the transprosthetic blood flow and ineffective anticoagulation. Genetic polymorphism of the genes VKORC1 (-1639 G > A and 1173 C > T), CYP2C9 (*2 & *3 alleles) and CYP4F2 (1347 G > A) are known to influence the anticoagulant dose-effect response. Since there has not been any earlier study on the direct influence of gene polymorphism on the development of PVT, we investigated into this association.Genotyping for the genes VKORC1, CYP2C9 and CYP4F2 was carried out by conventional PCR-RFLP method for 91 consecutive PVT patients. Subjects of our earlier study served as controls (n = 136).Female patients and patients with smaller prosthetic valve size were more prone to developing PVT (68%, n = 62). Patients bearing A allele of CYP4F2 1347 G > A polymorphism exhibited a fivefold increased risk of PVT (OR = 5.022 (1.39-18.04), P = .013). G allele of VKORC1 when analyzed in combination of genotypes showed a fourteen fold increased risk for developing PVT (OR = 14.25 (5.52-36.77), P = 0.001). CYP2C9 (*2&*3) gene polymorphism did not show any significant association with PVT (OR = 1.54 (0.128 - 18.82), P = .731).Patients bearing A allele of CYP4F2 showed an increased risk of developing PVT in our case - control study.
尽管在瓣膜设计和所用材料方面取得了进展，但人工瓣膜血栓形成（PVT）仍然是心脏机械瓣膜置换的严重并发症。影响PVT发生的因素包括：瓣膜的血栓形成倾向、人工瓣膜血流的血流动力学以及抗凝治疗无效。已知基因VKORC1（-1639 G＞A和1173 C＞T）、CYP2C9（2和3等位基因）和CYP4F2（1347 G＞A）的基因多态性会影响抗凝剂量效应反应。由于此前尚无关于基因多态性对PVT发生的直接影响的研究，我们对此关联进行了调查。
采用常规PCR-RFLP方法对91例连续的PVT患者进行了VKORC1、CYP2C9和CYP4F2基因的基因分型。我们早期研究的对象作为对照（n = 136）。
女性患者和人工瓣膜尺寸较小的患者更容易发生PVT（68%，n = 62）。携带CYP4F2 1347 G＞A多态性A等位基因的患者发生PVT的风险增加了五倍（OR = 5.022（1.39 - 18.04），P = .013）。当对VKORC1的G等位基因进行基因型组合分析时，发生PVT的风险增加了十四倍（OR = 14.25（5.52 - 36.77），P = 0.001）。CYP2C9（*2&*3）基因多态性与PVT未显示出任何显著关联（OR = 1.54（0.128 - 18.82），P = .731）。
在我们的病例对照研究中，携带CYP4F2 A等位基因的患者发生PVT的风险增加。
