The online version of this article (doi:10.1186/1475-2875-11-125) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
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.
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.
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.
Authors’ original file for figure 112936_2012_2074_MOESM1_ESM.pdf
Shimada T, Yamazaki H, Mimura M, Inui Y, Guengerich FP: Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther. 1994, 270: 414-423. PubMed
Garsa AA, McLeod HL, Marsh S: CYP3A4 and CYP3A5 genotyping by Pyrosequencing. BMC Med Genet. 2005, 9: 6-19.
Adjei GO, Kristensen K, Goka BQ, Hoegberg LC, Alifrangis M, Rodrigues OP, Kurtzhals JA: Effect of concomitant artesunate administration and cytochrome P4502C8 polymorphisms on the pharmacokinetics of amodiaquine in Ghanaian children with uncomplicated malaria. Antimicrob Agents Chemother. 2008, 52: 4400-4406. 10.1128/AAC.00673-07. PubMedCentralCrossRefPubMed
O'Connell KA, Gatakaa H, Poyer S, Njogu J, Evance I, Munroe E, Solomon T, Goodman C, Hanson K, Zinsou C, Akulayi L, Raharinjatovo J, Arogundade E, Buyungo P, Mpasela F, Adjibabi CB, Agbango JA, Ramarosandratana BF, Coker B, Rubahika D, Hamainza B, Chapman S, Shewchuk T, Chavasse D: Got ACTs? Availability, price, market share and provider knowledge of anti-malarial medicines in public and private sector outlets in six malaria-endemic countries. Malar J. 2011, 10: 326-10.1186/1475-2875-10-326. PubMedCentralCrossRefPubMed
Littrell M, Gatakaa H, Evance I, Poyer S, Njogu J, Solomon T, Munroe E, Chapman S, Goodman C, Hanson K, Zinsou C, Akulayi L, Raharinjatovo J, Arogundade E, Buyungo P, Mpasela F, Adjibabi CB, Agbango JA, Ramarosandratana BF, Coker B, Rubahika D, Hamainza B, Shewchuk T, Chavasse D, O'Connell KA: Monitoring fever treatment behaviour and equitable access to effective medicines in the context of initiatives to improve ACT access: baseline results and implications for programming in six African countries. Malar J. 2011, 10: 327-10.1186/1475-2875-10-327. PubMedCentralCrossRefPubMed
World Health Organization: World malaria report. Geneva. 2011
Sawadogo CW, Amood Al-Kamarany M, Al-Mekhlafi HM, Elkarbane M, Al-Adhroey AH, Cherrah Y, Bouklouze A: Quality of chloroquine tablets available in Africa. Ann Trop Med Parassito. 2011, 105:
Newton PN, Green MD, Mildenhall DC, Plancon A, Nettey H, Nyadong L, Hostetler DM, Swamidoss I, Harris GA, Powell K, Timmermans AE, Amin AA, Opuni SK, Barbereau S, Faurant C, Soong RC, Faure K, Thevanayagam J, Fernandes P, Kaur H, Angus B, Stepniewska K, Guerin PJ, Fernandez FM: Poor quality vital anti-malarials in Africa - an urgent neglected public health priority. Malar J. 2011, 10: 352-10.1186/1475-2875-10-352. PubMedCentralCrossRefPubMed
Romano R, Tabacchi F, Paganotti GM, Russo G, Gramolelli S, Marinucci F, Ceccherini-Nelli L, Coluzzi M: Evaluation of bloodsucking arthropod bite as possible risk co-factor in Human herpesvirus-8 transmission route. Parassitologia. 2010, 52: 417-422.
Romano R, Gramolelli S, Tabacchi F, Russo G, Verzaro S, Marinucci F, Paganotti GM, Gaeta A, Coluzzi M: Human Herpesvirus 8 (HHV-8): salivary shedding in mothers and children from Uganda: risk factors and clues about transmission. Prevention and Research. 2011, 1: 44-52.
Yeka A, Gasasira A, Mpimbaza A, Achan J, Nankabirwa J, Nsobya S, Staedke SG, Donnelly MJ, Wabwire-Mangen F, Talisuna A, Dorsey G, Kamya MR, Rosenthal PJ: Malaria in Uganda: challenges to control on the long road to elimination: I. Epidemiology and current control efforts. Acta Trop . 2012, 121: 184-195. PubMedCentralCrossRefPubMed
Echeverry DF, Holmgren G, Murillo C, Higuita JC, Björkman A, Gil JP, Osorio L: Short report: polymorphisms in the pfcrt and pfmdr1 genes of Plasmodium falciparum and in vitro susceptibility to amodiaquine and desethylamodiaquine. Am J Trop Med Hyg. 2007, 77: 1034-1038. PubMed
Andriantsoanirina V, Ratsimbasoa A, Bouchier C, Tichit M, Jahevitra M, Rabearimanana S, Raherinjafy R, Mercereau-Puijalon O, Durand R, Ménard D: Chloroquine clinical failures in P. falciparum malaria are associated with mutant Pfmdr-1, not Pfcrt in Madagascar. PLoS One. 2010, 5: e13281-10.1371/journal.pone.0013281. PubMedCentralCrossRefPubMed
Rason MA, Andrianantenaina HB, Ariey F, Raveloson A, Domarle O, Randrianarivelojosia M: Prevalent pfmdr1 n86y mutant Plasmodium falciparum in Madagascar despite absence of pfcrt mutant strains. Am J Trop Med Hyg. 2007, 76: 1079-1083. PubMed
- Distribution of human CYP2C8*2 allele in three different African populations
Giacomo M Paganotti
- BioMed Central
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