Cis-regulatory genetic variants in the CCR5 gene and natural HIV-1 control in black South Africans

Gemma W. Koor, Maria Paximadis, Anabela C.P. Picton, Fidan Karatas, Shayne A. Loubser, Weijing He, Sunil K. Ahuja, Richard E. Chaisson, Neil Martinson, Osman Ebrahim, Caroline T. Tiemessen

Research output: Contribution to journalArticle

Abstract

Studies have investigated CCR5 haplotypes (HHA, HHB, HHC, HHD, HHE, HHF*1, HHF*2, HHG*1, HHG*2), defined by seven 5′UTR single nucleotide polymorphisms (SNPs), CCR2-V64I and CCR5Δ32, in HIV-1 disease. CCR5 cis-regulatory regions were sequenced, CCR2-V64I and CCR5Δ32 genotyped, and compared in HIV-1-infected black South Africans: 71 HIV-1 controllers (23 elite controllers, 37 viraemic controllers (VCs), 11 high viral load long-term non-progressors) and 74 progressors. The HHE haplotype and 3′UTR +2919 T > G SNP heterozygosity were underrepresented in total controllers and VCs vs. progressors (p = .004; p = .007 and p = .002, pbonferroni = 0.032; p = .004, respectively). Possession of the +2919 T > G SNP (dominant mode) was associated with HIV-1 progression (controllers vs. progressors: p = .001, pbonferroni = 0.016). The +2919 T > G SNP is in linkage disequilibrium (LD; r2 = 0.73) with two 5′UTR SNPs (−2459G > A and -2135 T > C; r2 = 1: 5′UTR-2SNP-hap). The 5′UTR-2SNP-hap was lower in total controllers and VCs vs. progressors (p = .003, pbonferroni = 0.048; p = .01, respectively). Results suggest -2459G > A, −2135 T > C, and + 2919 T > G as key CCR5 variants in HIV-1 control.

Original languageEnglish (US)
Pages (from-to)16-24
Number of pages9
JournalClinical Immunology
Volume205
DOIs
StatePublished - Aug 2019

Keywords

  • CCR5
  • Cis-regulatory regions
  • Genetic variants
  • HIV-1
  • Natural control
  • South Africa

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Koor, G. W., Paximadis, M., Picton, A. C. P., Karatas, F., Loubser, S. A., He, W., Ahuja, S. K., Chaisson, R. E., Martinson, N., Ebrahim, O., & Tiemessen, C. T. (2019). Cis-regulatory genetic variants in the CCR5 gene and natural HIV-1 control in black South Africans. Clinical Immunology, 205, 16-24. https://doi.org/10.1016/j.clim.2019.05.009