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An insertion-deletion (indel) polymorphism within the 3′ untranslated region (UTR) of  HLA-C  has been shown to be involved in the regulation of HLA-C expression. Individuals who carry a deletion at this position exhibit increased HLA-C expression, which associates with lower viral set point in HIV-1 infected individuals. This  263  indel (rs67384697) is reported to be in strong linkage disequilibrium (LD) with a single nucleotide polymorphism (SNP) 35 kilobases upstream of  HLA-C  ( -35T/C ; rs9264942) in Caucasian individuals, making this SNP a potential marker for both HLA-C expression and HIV-1 disease progression. We therefore examined genetic variation within the  HLA-C  3′ UTR of 265 Black and Caucasian South Africans by direct sequencing and identified haplotypes encompassing the  263  indel and another indel at position 230 in both populations. Concomitant evaluation of variability at the  −35  SNP revealed this polymorphism to be an inappropriate marker for the  263  indel in these populations. These findings provide important insights into genetic variability within the regulatory regions of  HLA-C  that have potential implications for our understanding of the regulation of HLA-C expression and its impact on HIV-1 disease progression.

Genetic Variability in Markers of HLA-C Expression in Two Diverse South African Populations