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01.12.2012 | Research | Ausgabe 1/2012 Open Access

Malaria Journal 1/2012

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

Zeitschrift:
Malaria Journal > Ausgabe 1/2012
Autoren:
Giacomo M Paganotti, Silvia Gramolelli, Francesca Tabacchi, Gianluca Russo, David Modiano, Mario Coluzzi, Rita Romano
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1475-2875-11-125) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

GMP and RR conceived the study. GMP, FT, DM, MC and RR coordinated the study. GMP, SG and FT carried out the molecular genetic study, performed database and statistical analyses. GR carried out field surveys. GMP, SG, FT and RR drafted the manuscript. All authors read and approved the final manuscript.

Abstract

Background

The 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.

Methods

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).

Results

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.

Conclusions

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.
Zusatzmaterial
Authors’ original file for figure 1
12936_2012_2074_MOESM1_ESM.pdf
Literatur
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