Distribution of human CYP2C8*2 allele in three different African populations

Abstract

BackgroundThe aim of this study was to investigate cytochrome P450 2C8*2 (CYP2C8*2) 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.MethodsA 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).ResultsA 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.ConclusionsThis 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.

Priority pharmacogenetics for the African continent: focus on CYP450

“…As expected, decreased activity of CYP2C8 will result in an accumulation of amodiaquine, resulting in hepatotoxicity and agranulocytosis. It has also been reported recently [32] and confirmed by an independent group [33] that decreased CYP2C8 activity may result in a selective pressure resulting in the development of resistance to therapy by the Plasmodium parasite.…”

“…Senegal [32]. The fact that CYP2C8 data exists for populations in a mere seven African countries, does not allow for sufficient inference of the distribution of alleles across the continent.…”

Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions

“…Their frequencies differ significantly both between and within continental populations (Table 5 ancestry. In sub-Saharan African populations, its allele frequency ranges from about 0.10 in a Fulani population in Burkina Faso to 0.37 in a Mbuti pygmy population in Congo (Cavaco et al, 2005;Rower et al, 2005;Parikh et al, 2007;Kudzi et al, 2009;Speed et al, 2009;Paganotti et al, 2011Paganotti et al, , 20121000Genomes Project Consortium, 2012Arnaldo et al, 2013;Marwa et al, 2014). In an African-American population in the New York area, the allele frequency of CYP2C8*2 was 0.10 (Martis et al, 2013).…”

How polymorphisms of the cytochrome P450 genes affect ibuprofen and diclofenac metabolism and toxicity / Kako polimorfizmi gena citokroma P450 utječu na metabolizam i toksičnost ibuprofena i diklofenaka

“…These variants are responsible for interindividual and interethnic variability in drug response (36), since their frequencies vary significantly between races and population groups. Clinically the most important variants are CYP2C8*2 to *5 (37,38). The frequencies of the alleles *2, *3, and *4 are 0.3, 10.9, and 5.9 in Caucasians and 15.9, 0.0, 0.41 in Blacks, respectively, while in the Asians these variants have not been found, or are extremely low (39,40).…”