Mutations in c-c chemokine receptor type five ( ccr 5 ) in south african individuals

The importance of the CCR5 receptor in HIV infection and disease progression was recognized with the discovery of the Δ32 allele. Individuals homozygous for this mutation lack functional CCR5, and are almost completely resistant to HIV infection. Heterozygous individuals display decreased cell surface CCR5 which slows disease progression. Phenotypic expression of CCR5 is 2 heterogeneous and its relation to genetic mutations in the CCR5 gene is not currently known for the South African population. This provided the rationale for investigating genetic variation in low CCR5 expressers in South Africa. Flow cytometry was used to measure the phenotypic distribution of CCR5 in 245 individuals by assessing both the percentage of CD4CCR5 T-cells and CCR5 density. Genotypic data revealed 70 single nucleotide polymorphisms (SNPs), four insertions and the ∆32 deletion within the 65 individuals selected for sequencing. The ∆32 mutation was detected only in the Caucasian group and included a single homozygous individual with an absence of CCR5 expression. A total of eight previously described open reading frame (ORF) mutations were found in this study as well as twelve novel mutations with two in the ORF. Greater genetic diversity was present in the Black South African group, with 39 mutations being exclusive to this group.