PCSK9、WDR12、CDKN2A和CXCL12基因多态性对约旦心血管疾病患者华法林反应性和敏感性的影响
Impact of PCSK9, WDR12, CDKN2A, and CXCL12 Polymorphisms in Jordanian Cardiovascular Patients on Warfarin Responsiveness and Sensitivity.
作者信息
Ibdah Rasheed K, Al-Eitan Laith N, Alrabadi Nasr N, Almasri Ayah Y, Alnaamneh Adan H, Khasawneh Rame H, Alghamdi Mansour A
机构信息
Division of Cardiology, Department of Internal Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan.
Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid, Jordan.
出版信息
Int J Gen Med. 2021 Jan 14;14:103-118. doi: 10.2147/IJGM.S287238. eCollection 2021.
BACKGROUND
The main objective of this study is sought to determine the impacts of PCSK9, WDR12, CDKN2A, and CXCL12 polymorphisms on warfarin sensitivity and responsiveness in Jordanian cardiovascular patients during the initiation and stabilization phases of therapy.
METHODS
This study took place at the anticoagulation clinic at Queen Alia Heart Institute (QAHI) in Jordan. DNA samples were collected from 212 cardiovascular patients and 213 healthy controls. Genomic SNPs genotyping was conducted using the MassARRAY System at the Australian Genome Research Facility.
RESULTS
This study assessed 10 polymorphisms (rs11206510 within the gene, rs6725887 and rs7582720 within the gene, rs4977574, rs10757278, and rs1333049 within the gene, rs2862116, rs7906426, rs1746048, and rs268322 within the gene) in 212 Jordanian cardiovascular patients. Carriers of CDKN2A rs1333049, rs10757278, and PCSK9 rs11206510 polymorphisms had an increased risk of resistance during the initiation phase of warfarin therapy compared to those who do not carry it, or those who are carrying one polymorphism only (P < 0.05), while carriers of CXCL12 rs7906426 polymorphism had similar increased risk but during the stabilization phase of warfarin therapy (P < 0.05).
CONCLUSION
Carriers of CXCL12 rs2862116 polymorphism had an increased risk to be warfarin extensive responders compared to those with no or only one polymorphism (P = 0.01). However, the presence of PCSK9 rs11206510 polymorphism affects the warfarin maintenance doses (P ˃ 0.0001).
背景
本研究的主要目的是确定在约旦心血管疾病患者的华法林治疗起始和稳定阶段，前蛋白转化酶枯草溶菌素9（PCSK9）、WD重复结构域12（WDR12）、细胞周期蛋白依赖性激酶抑制剂2A（CDKN2A）和CXC趋化因子配体12（CXCL12）基因多态性对华法林敏感性和反应性的影响。
方法
本研究在约旦阿莉亚王后心脏研究所（QAHI）的抗凝门诊进行。收集了212例心血管疾病患者和213例健康对照者的DNA样本。在澳大利亚基因组研究设施使用MassARRAY系统进行基因组单核苷酸多态性（SNP）基因分型。
结果
本研究评估了212例约旦心血管疾病患者的10种多态性（基因内的rs11206510、基因内的rs6725887和rs7582720、基因内的rs4977574、rs10757278和rs1333049、基因内的rs2862116、rs7906426、rs1746048和rs268322）。与未携带CDKN2A基因rs1333049、rs10757278多态性或仅携带一种多态性的患者相比，携带这些多态性的患者在华法林治疗起始阶段出现抵抗的风险增加（P<0.05），而携带CXCL12基因rs7906426多态性的患者在华法林治疗稳定阶段出现类似的风险增加（P<0.05）。
结论
与未携带或仅携带一种多态性的患者相比，携带CXCL12基因rs2862116多态性的患者成为华法林广泛反应者的风险增加（P = 0.01）。然而，PCSK9基因rs11206510多态性的存在会影响华法林的维持剂量（P＞0.0001）。
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