Department of Public Health and Infectious Diseases, La Sapienza University, Rome, Italy.
J Infect Dis. 2011 Dec 1;204(11):1772-8. doi: 10.1093/infdis/jir629. Epub 2011 Oct 12.
One approach to investigate if human genetic variation influences the selection of Plasmodium falciparum drug resistance is to compare the frequency of resistant infections among human populations differing in their genetic background and living in the same epidemiological context. A further complementary approach consists in comparing drug resistance among subjects differing for genes involved in drug metabolism. Here we report, from malariological surveys performed in Burkina Faso, that the prevalence of P. falciparum chloroquine-resistant infections (pfcrt 76T and/or pfmdr1 86Y alleles) differs among sympatric ethnic groups, being higher in the Mossi and Rimaibé groups than in the Fulani group (odds ratio [OR], 2.24; 95% confidence interval [CI], 1.27-3.92; P = .007). The association analysis revealed that the human CYP2C8*2 variant, known to determine a poor drug metabolizer phenotype, was associated with P. falciparum chloroquine-resistant infections (OR, 1.66; 95% CI, 1.13-2.43; P = .008). This variant is more frequent in the Mossi-Rimaibé group (23.7% ± 1.4%) than in the Fulani group (9.9% ± 2.5%; P = .0003). This study provides an example of how host genetic variation may influence the selection dynamics of a pathogen's drug resistance.
一种研究人类遗传变异是否影响疟原虫药物抗性选择的方法是比较具有不同遗传背景且生活在相同流行病学环境中的人群中耐药感染的频率。另一种补充方法是比较药物代谢相关基因不同的个体之间的药物耐药性。在这里，我们报告了在布基纳法索进行的疟疾调查结果，表明恶性疟原虫氯喹耐药感染（pfcrt 76T 和/或 pfmdr1 86Y 等位基因）在同域的族群中存在差异，莫西和里马比族群的患病率高于富拉尼族群（比值比 [OR]，2.24；95%置信区间 [CI]，1.27-3.92；P =.007）。关联分析表明，已知导致不良药物代谢表型的人类 CYP2C8*2 变体与恶性疟原虫氯喹耐药感染有关（OR，1.66；95% CI，1.13-2.43；P =.008）。该变体在莫西-里马比族群（23.7%±1.4%）中比富拉尼族群（9.9%±2.5%；P =.0003）更为常见。这项研究提供了一个宿主遗传变异如何影响病原体药物抗性选择动态的例子。
