Macêdo Marielle M, Almeida Anne C G, Silva Gabrielly S, Oliveira Amanda C, Mwangi Victor I, Shuan Ana C, Barbosa Laila R A, Rodrigues-Soares Fernanda, Melo Gisely C
Programa de Pós-graduação em Ciências Aplicadas à Hematologia, Universidade do Estado do Amazonas, Manaus 69040-000, AM, Brazil.
Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus 69040-000, AM, Brazil.
Pathogens. 2023 Jun 30;12(7):895. doi: 10.3390/pathogens12070895.
In the Amazon, the treatment for is chloroquine plus primaquine. However, this regimen is limited due to the risk of acute hemolytic anemia in glucose-6-phosphate dehydrogenase deficiency. Primaquine is a prodrug that requires conversion by the CYP2D6 enzyme to be effective against malaria. A series of cases were performed at an infectious diseases reference hospital in the Western Brazilian Amazon. The STANDARD G6PD (SD Biosensor) assay was used to infer G6PD status and real-time PCR to genotype , and CYP3A4. Eighteen patients were included, of which 55.6% had African A- variant (G202A/A376G), 11.1% African A+ variant (A376G), 5.6% Mediterranean variant (C563T) and 27.8% were wild type. CYP2C19, CYP2D6 and CYP3A4 genotyping showed no statistically significant differences in the frequency of star alleles between the groups G6PD deficient and G6PD normal. Elevated levels of liver and kidney markers in the G6PDd patients were observed in gNM, gRM and gUM of CYP2C19 and CYP2D6 ( < 0.05). Furthermore, in this study there was no influence of CYPs on hemolysis. These findings reinforce the importance of studies on the mapping of G6PD deficiency and genetic variations of CYP2C19, CYP2D6 and CYP3A4. This mapping will allow us to validate the prevalence of CYPs and determine their influence on hemolysis in patients with malaria, helping to decide on the treatment regimen.
在亚马逊地区，疟疾的治疗方法是氯喹加伯氨喹。然而，由于葡萄糖-6-磷酸脱氢酶缺乏症患者存在急性溶血性贫血的风险，这种治疗方案受到限制。伯氨喹是一种前体药物，需要通过CYP2D6酶转化才能有效对抗疟疾。在巴西亚马逊西部的一家传染病参考医院进行了一系列病例研究。使用标准G6PD（SD生物传感器）检测来推断G6PD状态，并通过实时PCR对CYP2C19、CYP2D6和CYP3A4进行基因分型。纳入了18名患者，其中55.6%为非洲A-变体（G202A/A376G），11.1%为非洲A+变体（A376G），5.6%为地中海变体（C563T），27.8%为野生型。CYP2C19、CYP2D6和CYP3A4基因分型显示，G6PD缺乏组和G6PD正常组之间的星等位基因频率没有统计学上的显著差异。在CYP2C19和CYP2D6的gNM、gRM和gUM中，观察到G6PDd患者的肝肾功能指标升高（P<0.05）。此外，在本研究中，细胞色素P450对溶血没有影响。这些发现强化了对G6PD缺乏症以及CYP2C19、CYP2D6和CYP3A4基因变异进行图谱研究的重要性。这种图谱研究将使我们能够验证细胞色素P450的流行情况，并确定它们对疟疾患者溶血的影响，有助于确定治疗方案。
