| Summary: | Genetic variation plays an important role in determining an individual’s
susceptibility to infectious disease. PSIP1 encodes LEDGF/p75, which stably
associates with the core domain of HIV-1 integrase via a highly-conserved
integrase binding domain (IBD) located in its C-terminal. Through this
interaction, the protein tethers HIV-1 IN to chromosomes at sites corresponding to
regions of high LEDGF/p75-mediated transcription. Genetic variation within
PSIP1 was identified and characterized in black South Africans to establish
whether variation in this influences an individual’s susceptibility to HIV infection.
PCR assays were designed to amplify regions within the upstream non-coding
region, IBD and DNA-binding domains of the gene and selected polymorphisms
were then genotyped using allele-specific PCR, RFLP-PCR and
Pyrosequencing™ assays. Three insertion-deletion (indel) and eight single
nucleotide polymorphisms (SNP) where identified through sequencing. Four of
the SNPs had been recorded previously, while the seven other polymorphisms had
not and appear to be unique to our population. Differences in allelic and genotypic
frequencies where found between the various ethnic groups represented in this
study, which were reflected in the underlying haplotype structure within this gene,
suggesting that genetic substructure exists within the black South African
population. Differences in allele and genotype frequencies were also seen between
HIV+ individuals and the general population. Thus variation within PSIP1 may
influence an individual’s susceptibility to HIV-1 infectivity and/or rate of disease progression.
|
|---|
