Thailand Center of Excellence on Drug Discovery and Development, Thammasat University, Rangsit Campus, Klong Luang District, Pathumtani, Thailand; Mae-Sot General Hospital, Mae-Sot, Tak Province, Thailand.
Am J Trop Med Hyg. 2011 Sep;85(3):568-72. doi: 10.4269/ajtmh.2011.11-0194.
The aim of this study was to investigate the association between genetic polymorphisms of Plasmodium falciparum chloroquine resistance transporter (pfcrt), P. falciparum multidrug resistance 1 (pfmdr1), and P. falciparum ATPase (pfatp6) and clinical outcome after a three-day mefloquine-artesunate combination therapy in 134 patients with uncomplicated Plasmodium falciparum malaria in an area with multidrug resistance along the Thailand-Myanmar border. Analysis of gene mutation and amplification were performed by nested real-time polymerase chain reaction and SYBR Green I real-time polymerase chain reaction, respectively. The mutation for pfcrt (codons 76, 220, 271, 326, 356, and 371) was found in all isolates (100%), whereas no mutation of pfmdr1 (codon 86) and pfatp6 (codons 37, 693, 769, 898) was found. The Pfmdr1 copy number was significantly higher in isolates with recrudescence (median number = 2.44) compared with a sensitive response (median number = 1.44). The gene copy number was also found to be significantly higher in paired isolates collected before treatment and at the time of recrudescence. All isolates carried one pfatp6 gene copy.
本研究旨在调查在泰国-缅甸边境地区多药耐药区 134 例无并发症恶性疟原虫感染患者中，疟原虫氯喹耐药转运蛋白（pfcrt）、疟原虫多药耐药 1 基因（pfmdr1）和疟原虫 ATP 酶（pfatp6）的基因多态性与 3 天甲氟喹-青蒿琥酯联合治疗临床结局的相关性。通过巢式实时聚合酶链反应和 SYBR Green I 实时聚合酶链反应分别进行基因突变和扩增分析。所有分离株均发现 pfcrt（密码子 76、220、271、326、356 和 371）发生突变（100%），而 pfmdr1（密码子 86）和 pfatp6（密码子 37、693、769、898）未发生突变。复发组 Pfmdr1 拷贝数（中位数=2.44）明显高于敏感反应组（中位数=1.44）。在治疗前和复发时采集的配对分离株中，基因拷贝数也明显更高。所有分离株均携带一个 pfatp6 基因拷贝。
