TY - JOUR
T1 - Cis-regulatory genetic variants in the CCR5 gene and natural HIV-1 control in black South Africans
AU - Koor, Gemma W.
AU - Paximadis, Maria
AU - Picton, Anabela C.P.
AU - Karatas, Fidan
AU - Loubser, Shayne A.
AU - He, Weijing
AU - Ahuja, Sunil K.
AU - Chaisson, Richard E.
AU - Martinson, Neil
AU - Ebrahim, Osman
AU - Tiemessen, Caroline T.
N1 - Funding Information:
CT, MP, AP – conception and design of the study. NM, RC, OE – recruitment of patients. GK, MP, AP, FK – acquisition of data and analysis. GK, MP – interpretation of data. SL, MP – design of an assay. GK, MP – drafting the article. MP, CT, WH, SA – revising it critically for important intellectual content. MP, CT – final approval of the version to be submitted. This work is based on the research supported by grants awards from the Strategic Health Innovation Partnerships (SHIP) Unit of the South African Medical Research Council, a grantee of the Bill & Melinda Gates Foundation, and the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa. The Longitudinal Study of HIV-Associated Lung Infections in Soweto (progressor group) was funded by the National Institutes of Health, USA (R01HL090312 and P30AI094189: R. E. Chaisson). None of the authors have any potential financial conflicts of interest related to this manuscript.
Funding Information:
This work is based on the research supported by grants awards from the Strategic Health Innovation Partnerships (SHIP) Unit of the South African Medical Research Council , a grantee of the Bill & Melinda Gates Foundation , and the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa. The Longitudinal Study of HIV-Associated Lung Infections in Soweto (progressor group) was funded by the National Institutes of Health , USA ( R01HL090312 and P30AI094189 : R. E. Chaisson).
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/8
Y1 - 2019/8
N2 - 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.
AB - 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.
KW - CCR5
KW - Cis-regulatory regions
KW - Genetic variants
KW - HIV-1
KW - Natural control
KW - South Africa
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U2 - 10.1016/j.clim.2019.05.009
DO - 10.1016/j.clim.2019.05.009
M3 - Article
C2 - 31100442
AN - SCOPUS:85065842557
SN - 1521-6616
VL - 205
SP - 16
EP - 24
JO - Clinical Immunology
JF - Clinical Immunology
ER -