1. A HIGH FREQUENCY OF APOBEC3G POLYMORPHISM IN HIV+ SOUTH AFRICAN POPULATION Dr Nyasha Chin’ombe, UCT, South Africa AIDS restriction genes in Africans

2. Scope of HIV in Africa HIV/AIDS remains a public health problem in Africa. In South Africa alone, about 5.7million people are estimated to be living with HIV.

3. AIDS restriction genes AIDS restriction genes – are host genes that affect HIV/AIDS disease outcomes – eg infection, susceptibility or disease progression

4. AIDS restriction genes versus HIV Host genes attempting to stop virus Virus attempting to complete its cycle

5. APOBEC3G the APOBEC (apolipoprotein B mRNA-editing enzyme catalytic polypeptide) family are known to influence susceptibility to HIV infection APOBEC3G induces G-to-A hypermutation in the HIV genome by deaminating cytidine to uridine thereby inhibiting viral replication and decelerating disease progression. A polymorphism APOBEC3G gene (A-to-G base change) in which histidine mutates to arginine (H186R) results in reduced APOBEC activity. Frequency is 0.37 in African-Americans & 0.03 in Caucasians

6. Objective To establish the allele frequency of the APOBEC3G genotype in samples of South African and other African populations

7. Materials & Methods Study subjects 1.HIV+ South African cohort 2.HIV+ Malawian cohort 3.HIV+ Zimbabwean cohort infants 4.Cameroun infants (HIV-status unknown) Study subjects 1.HIV+ South African cohort 2.HIV+ Malawian cohort 3.HIV+ Zimbabwean cohort infants 4.Cameroun infants (HIV-status unknown) Methods Isolated DNA from blood PCR of APOBEC3G region Digestion by HhaI enzyme Methods Isolated DNA from blood PCR of APOBEC3G region Digestion by HhaI enzyme

8. RESULTS Example of RFLP gel for genotyping AA: homozygous normal AG: heterozygous GG: homozygous mutant Example of RFLP gel for genotyping AA: homozygous normal AG: heterozygous GG: homozygous mutant

9. APOBEC3G in South African sample The G allele frequency was 34% and is comparable to what has previously been found in African Americans (37%), above what has been found in Caucasians (3%) GENOTYPEAA (HH)AG (HR)GG (RR) NUMBER (n=305)13613336 FREQUENCY(%)44.6%43.6%11.8% alleleAG frequency0.660.34

10. APOBEC3G in Malawian sample GENOTYPEAAAGGG NUMBER (n=187)698830 FREQ(%)36.9%47.0%16.0% alleleAG frequency0.600.40

11. APOBEC3G in Zimbabwean sample GENOTYPEAAAGGG NUMBER (n=91)334216 FREQ(%)36.3%46.2%17.6% alleleAG frequency0.590.41

12. APOBEC3G in West African sample GENOTYPEAAAGGG NUMBER (n=63)163413 FREQ(%)44.4%54.0%20.6% alleleAG frequency0.520.48

13. On top of APOBEC3G We have also found the presence of other gene variants such as RANTES In1.1C and IL-10 -595A and these may also be predisposing Africans to HIV infection

14. Conclusions & Recommendations High allele frequency of APOBEC3G variant could be predisposing Africans to HIV infection High frequency of the gene variant may also be accelerating AIDS disease progression in Africans Need for further research in other AIDS restriction genes in Africans

15. Acknowledgements UCT Pharmacogenomics Group Zimbabwean collaborators Malawian collaborators Ambroise Wonkam & Cameroun collaborators Claude Leon Foundation – my fellowship