Thursday, June 19, 2008

Database and clinical implications of African genetic diversity

Establishment of a biobank and pharmacogenetics database of African populations
Alice Matimba, Margaret N Oluka, Benjamin U Ebeshi, Jane Sayi, Oluseye O Bolaji, Anastasia N Guantai and Collen M Masimirembwa
European Journal of Human Genetics (2008) 16, 780–783

There's no abstract, so here are the more more interesting parts:
We here report the results of the first phase of this initiative that has seen research groups from five different African countries with collaborative support from leading experts in Europe and America establish a biobank of blood and DNA from nine ethnic groups from across the African continent. The biobank of anonymous samples has been used to establish baseline frequency distribution of SNPs of genes important in drug metabolism, hence the initiation of a pharmacogenetics database (
The biobank consists of 1488 DNA samples from nine ethnic groups (Yoruba, Hausa, Ibo, Luo, Kikuyu, Maasai, Shona, San and Venda)
regarding within-Africa diversity:
We further analyzed the data for possible stratification of the African ethnic groups alone. No distinct differentiation was observed. Studies using other genetic markers have demonstrated that there is great genetic diversity among African populations compared to Caucasian or Oriental populations.12 These preliminary findings from our studies could indicate that the number and/or type of genes and/or SNPs analyzed do not carry enough resolution power to capture the genetic diversity of African populations reported in other studies.
some clinical implications:
The high frequency of individuals who are homozygous for the CYP2B6*6 allele (18–25% ) in African populations is predictive of reduced capacity to metabolize and dispose efavirenz compared to Caucasians where lower genotype frequencies of 5–10% have been reported.17, 18 This is in agreement with clinical observations in which Africans have been reported to have significantly higher plasma concentrations of the drug compared to Caucasians when given at the standard 600 mg per day doses.19 Ongoing studies in our laboratory in HIV/AIDS patients taking the anti-HIV drug, efavirenz, indicate the need to lower the dose of this drug in people of African origin homozygous for the CYP2B6*6 allele (Nyakutira et al, unpublished). This could go a long way in reducing adverse effects hence increase treatment compliance. This could also reduce the costs for individuals requiring lower doses and thus partly contributes to the diagnostic costs of identifying such individuals. For the African specific CYP2D6*17 variant20 similar clinical effects could be explored in the use of antipsychotic drugs21, 22 in African populations based on the observed high frequency of the variant (14–34% ) across the major African populations reported in this study (Table 1). Though the current pharmacogenetics database carries no direct phenotype information linked to carriers of the variants, clinical extrapolations from well-established in vivo effects of these polymorphisms give an important baseline that can be the basis for population-specific clinical trial design for optimal use of some medicines.

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