Department of Public Health and Infectious Diseases, Sapienza University, P. le Aldo Moro 5, 00185 Rome, Italy.
Malar J. 2012 Apr 25;11:125. doi: 10.1186/1475-2875-11-125.
The aim of this study was to investigate cytochrome P450 2C82 (CYP2C82) distribution and allele frequency in three populations from West and East Africa exposed to Plasmodium falciparum malaria. CYP2C8 enzyme is involved in the metabolism of the anti-malarials amodiaquine and chloroquine. The presence of the CYP2C8*2 defective allele has been recently associated to higher rate of chloroquine-resistant malaria parasites.
A total of 503 young subjects were genotyped for the single nucleotide polymorphism rs11572103 (A/T). Eighty-eight were from southern Senegal, 262 from eastern Uganda and 153 from southern Madagascar. The PCR-RFLP technique was used to discriminate the wild-type (A) from the defective allele (T).
A CYP2C8*2 (T) allele frequency of 0.222 ± 0.044 was detected in Senegal, 0.105 ± 0.019 in Uganda and 0.150 ± 0.029 in Madagascar.
This study demonstrated that CYP2C8*2 allele is widespread in Africa. This allele occurs at different frequency in West and East Africa, being higher in Senegal than in Uganda and Madagascar. These data indicate that an important fraction of the populations analysed has a decreased enzymatic activity, thus being at higher risk for drug accumulation with two possible consequences: i) an exacerbation of drug-associated adverse side effects; ii) an increase of drug-resistance selection pressure on P. falciparum parasites.
本研究旨在调查暴露于恶性疟原虫中的来自西非和东非的三个人群中细胞色素 P450 2C82（CYP2C82）的分布和等位基因频率。CYP2C8 酶参与抗疟药阿莫地喹和氯喹的代谢。最近发现 CYP2C8*2 缺陷等位基因的存在与更高的氯喹耐药疟原虫率有关。
共对来自塞内加尔南部的 88 人、乌干达东部的 262 人和马达加斯加南部的 153 人进行了单核苷酸多态性 rs11572103（A/T）的基因分型。PCR-RFLP 技术用于区分野生型（A）和缺陷型等位基因（T）。
在塞内加尔、乌干达和马达加斯加，CYP2C8*2（T）等位基因频率分别为 0.222±0.044、0.105±0.019 和 0.150±0.029。
本研究表明 CYP2C8*2 等位基因在非洲广泛存在。该等位基因在西非和东非的频率不同，在塞内加尔的频率高于乌干达和马达加斯加。这些数据表明，分析的人群中有相当一部分人的酶活性降低，因此更容易发生药物蓄积，可能有两个后果：i）药物相关不良反应加重；ii）增加对恶性疟原虫的耐药选择压力。
