title: Human genetic variation is associated with Plasmodium falciparum drug resistance.
abstract: 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.
authors: Department of Public Health and Infectious Diseases, La Sapienza University, Rome, Italy. giacomo.paganotti@uniroma1.it
authors: Giacomo M
authors: GM
authors: Paganotti
authors: Baba C
authors: BC
authors: Gallo
authors: Federica
authors: F
authors: Verra
authors: Bienvenu S
authors: BS
authors: Sirima
authors: Issa
authors: I
authors: Nebié
authors: Amidou
authors: A
authors: Diarra
authors: Mario
authors: M
authors: Coluzzi
authors: David
authors: D
authors: Modiano
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000962:Antimalarials / Q000494:pharmacology; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044383:Black People / Q000235:genetics*; D002050:Burkina Faso / Q000453:epidemiology; D002648:Child; D002738:Chloroquine / Q000494:pharmacology; D003430:Cross-Sectional Studies; D065727:Cytochrome P-450 CYP2C8; D004351:Drug Resistance / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D016778:Malaria, Falciparum / Q000208:ethnology / Q000235:genetics* / Q000469:parasitology; D026901:Membrane Transport Proteins / Q000235:genetics; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D015995:Prevalence; D015800:Protozoan Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: D000962:Antimalarials; D001189:Aryl Hydrocarbon Hydroxylases; D002738:Chloroquine; D065727:Cytochrome P-450 CYP2C8; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015800:Protozoan Proteins; C513498:Mdr1 protein, Plasmodium falciparum; C416369:PfCRT protein, Plasmodium falciparum; C450259:CYP2C8 protein, human