Impact of polymorphisms in the HCP5 and HLA-C, and ZNRD1 genes on HIV viral load

Lise Wegner Thørner, Christian Erikstrup, Lene Holm Harritshøj, Margit Hørup Larsen, Gitte Kronborg, Court Pedersen, Carsten Schade Larsen, Gitte Pedersen, Jan Gerstoft, Niels Obel, Henrik Ullum

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Abstract

AIMS: Single nucleotide polymorphisms (SNPs) in the human leucocyte antigen (HLA) complex P5 (HCP5), HLA-C, and near the zinc ribbon domain containing 1 (ZNRD1) have been shown to influence viral load (VL) set point in HIV-infected individuals with a known seroconversion onset. We aimed to determine the influence of HCP5 rs2395029, HLA-C rs9264942, and ZNRD1 rs3869068 on VL in antiretroviral-naïve individuals and on time to the first VL<51 copies/ml and on CD4(+) T-cell recovery after initiation of combination antiretroviral therapy (cART).

MATERIAL AND METHODS: We genotyped the rs2395029 (A>C), rs9264942 (T>C), and rs3869068 (C>T) SNPs in 1897 Caucasians from The Danish HIV Cohort Study - a prospective, nationwide, population-based study of HIV-infected individuals in Denmark. General linear models evaluated the effect of SNPs on VL in antiretroviral-naïve individuals 0-18months after diagnosis and on CD4(+) T-cell recovery during cART. Cox proportional hazard regression analysis assessed the association with time to first VL<51 copies/ml. All models were assuming additive genetic effects.

RESULTS: The rs2395029, rs9264942, and rs3869068 minor alleles were associated with lower VL in antiretroviral-naïve individuals (rs2395029: [mean VL (copies/ml)], A/A: 70,795 [61,660-79,433], A/C: 33,884 [19,498-58,884], P=0.002; rs9264942: TT: 81,283 [67,608-97,724], T/C: 63,096 [54,954-75,858], CC: 38,905 [25,119-58,884], P<0.0001; rs3869068, CC: 72,444 [63,096-83,176], C/T: 45,709 [33,113-64,565], TT: 58,884 [20,417-169,824], P=0.01). Moreover, the C-alleles of rs2395029 and rs9264942 were associated with shorter time to VL<51 copies/ml: (HR [95% confidence interval], 1.67 [1.09-1.72], P=0.008; 1.16 [1.06-1.28], P=0.002; 1.30 [1.08-1.53], P=0.005, respectively, adjusted for last VL before cART). None of the SNPs predicted CD4(+) T-cell recovery during cART.

CONCLUSIONS: The minor alleles of rs2395029, rs9264942, and rs3689068 associate with lower VL among antiretroviral-naïve individuals and with shorter time to first VL<51copies/ml during cART even after adjustment for VL before cART.

Original languageEnglish
JournalInfection, Genetics and Evolution
Volume41
Pages (from-to)185-190
ISSN1567-1348
DOIs
Publication statusPublished - Jul 2016

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human immunodeficiency virus
viral load
antigen
Viral Load
Zinc
polymorphism
zinc
HIV
genetic polymorphism
allele
gene
genes
single nucleotide polymorphism
Single Nucleotide Polymorphism
confidence interval
regression analysis
Alleles
alleles
hazard
HLA antigens

Keywords

  • Journal Article

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Thørner, L. W., Erikstrup, C., Harritshøj, L. H., Larsen, M. H., Kronborg, G., Pedersen, C., ... Ullum, H. (2016). Impact of polymorphisms in the HCP5 and HLA-C, and ZNRD1 genes on HIV viral load. Infection, Genetics and Evolution, 41, 185-190. https://doi.org/10.1016/j.meegid.2016.03.037
Thørner, Lise Wegner ; Erikstrup, Christian ; Harritshøj, Lene Holm ; Larsen, Margit Hørup ; Kronborg, Gitte ; Pedersen, Court ; Larsen, Carsten Schade ; Pedersen, Gitte ; Gerstoft, Jan ; Obel, Niels ; Ullum, Henrik. / Impact of polymorphisms in the HCP5 and HLA-C, and ZNRD1 genes on HIV viral load. In: Infection, Genetics and Evolution. 2016 ; Vol. 41. pp. 185-190.
@article{e0b4cba7cdf149ec9306b919d3a88c81,
title = "Impact of polymorphisms in the HCP5 and HLA-C, and ZNRD1 genes on HIV viral load",
abstract = "AIMS: Single nucleotide polymorphisms (SNPs) in the human leucocyte antigen (HLA) complex P5 (HCP5), HLA-C, and near the zinc ribbon domain containing 1 (ZNRD1) have been shown to influence viral load (VL) set point in HIV-infected individuals with a known seroconversion onset. We aimed to determine the influence of HCP5 rs2395029, HLA-C rs9264942, and ZNRD1 rs3869068 on VL in antiretroviral-na{\"i}ve individuals and on time to the first VL<51 copies/ml and on CD4(+) T-cell recovery after initiation of combination antiretroviral therapy (cART).MATERIAL AND METHODS: We genotyped the rs2395029 (A>C), rs9264942 (T>C), and rs3869068 (C>T) SNPs in 1897 Caucasians from The Danish HIV Cohort Study - a prospective, nationwide, population-based study of HIV-infected individuals in Denmark. General linear models evaluated the effect of SNPs on VL in antiretroviral-na{\"i}ve individuals 0-18months after diagnosis and on CD4(+) T-cell recovery during cART. Cox proportional hazard regression analysis assessed the association with time to first VL<51 copies/ml. All models were assuming additive genetic effects.RESULTS: The rs2395029, rs9264942, and rs3869068 minor alleles were associated with lower VL in antiretroviral-na{\"i}ve individuals (rs2395029: [mean VL (copies/ml)], A/A: 70,795 [61,660-79,433], A/C: 33,884 [19,498-58,884], P=0.002; rs9264942: TT: 81,283 [67,608-97,724], T/C: 63,096 [54,954-75,858], CC: 38,905 [25,119-58,884], P<0.0001; rs3869068, CC: 72,444 [63,096-83,176], C/T: 45,709 [33,113-64,565], TT: 58,884 [20,417-169,824], P=0.01). Moreover, the C-alleles of rs2395029 and rs9264942 were associated with shorter time to VL<51 copies/ml: (HR [95{\%} confidence interval], 1.67 [1.09-1.72], P=0.008; 1.16 [1.06-1.28], P=0.002; 1.30 [1.08-1.53], P=0.005, respectively, adjusted for last VL before cART). None of the SNPs predicted CD4(+) T-cell recovery during cART.CONCLUSIONS: The minor alleles of rs2395029, rs9264942, and rs3689068 associate with lower VL among antiretroviral-na{\"i}ve individuals and with shorter time to first VL<51copies/ml during cART even after adjustment for VL before cART.",
keywords = "Journal Article",
author = "Th{\o}rner, {Lise Wegner} and Christian Erikstrup and Harritsh{\o}j, {Lene Holm} and Larsen, {Margit H{\o}rup} and Gitte Kronborg and Court Pedersen and Larsen, {Carsten Schade} and Gitte Pedersen and Jan Gerstoft and Niels Obel and Henrik Ullum",
note = "Copyright {\circledC} 2016 Elsevier B.V. All rights reserved.",
year = "2016",
month = "7",
doi = "10.1016/j.meegid.2016.03.037",
language = "English",
volume = "41",
pages = "185--190",
journal = "Infection, Genetics and Evolution",
issn = "1567-1348",
publisher = "Elsevier",

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Thørner, LW, Erikstrup, C, Harritshøj, LH, Larsen, MH, Kronborg, G, Pedersen, C, Larsen, CS, Pedersen, G, Gerstoft, J, Obel, N & Ullum, H 2016, 'Impact of polymorphisms in the HCP5 and HLA-C, and ZNRD1 genes on HIV viral load', Infection, Genetics and Evolution, vol. 41, pp. 185-190. https://doi.org/10.1016/j.meegid.2016.03.037

Impact of polymorphisms in the HCP5 and HLA-C, and ZNRD1 genes on HIV viral load. / Thørner, Lise Wegner; Erikstrup, Christian; Harritshøj, Lene Holm; Larsen, Margit Hørup; Kronborg, Gitte; Pedersen, Court; Larsen, Carsten Schade; Pedersen, Gitte; Gerstoft, Jan; Obel, Niels; Ullum, Henrik.

In: Infection, Genetics and Evolution, Vol. 41, 07.2016, p. 185-190.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Impact of polymorphisms in the HCP5 and HLA-C, and ZNRD1 genes on HIV viral load

AU - Thørner, Lise Wegner

AU - Erikstrup, Christian

AU - Harritshøj, Lene Holm

AU - Larsen, Margit Hørup

AU - Kronborg, Gitte

AU - Pedersen, Court

AU - Larsen, Carsten Schade

AU - Pedersen, Gitte

AU - Gerstoft, Jan

AU - Obel, Niels

AU - Ullum, Henrik

N1 - Copyright © 2016 Elsevier B.V. All rights reserved.

PY - 2016/7

Y1 - 2016/7

N2 - AIMS: Single nucleotide polymorphisms (SNPs) in the human leucocyte antigen (HLA) complex P5 (HCP5), HLA-C, and near the zinc ribbon domain containing 1 (ZNRD1) have been shown to influence viral load (VL) set point in HIV-infected individuals with a known seroconversion onset. We aimed to determine the influence of HCP5 rs2395029, HLA-C rs9264942, and ZNRD1 rs3869068 on VL in antiretroviral-naïve individuals and on time to the first VL<51 copies/ml and on CD4(+) T-cell recovery after initiation of combination antiretroviral therapy (cART).MATERIAL AND METHODS: We genotyped the rs2395029 (A>C), rs9264942 (T>C), and rs3869068 (C>T) SNPs in 1897 Caucasians from The Danish HIV Cohort Study - a prospective, nationwide, population-based study of HIV-infected individuals in Denmark. General linear models evaluated the effect of SNPs on VL in antiretroviral-naïve individuals 0-18months after diagnosis and on CD4(+) T-cell recovery during cART. Cox proportional hazard regression analysis assessed the association with time to first VL<51 copies/ml. All models were assuming additive genetic effects.RESULTS: The rs2395029, rs9264942, and rs3869068 minor alleles were associated with lower VL in antiretroviral-naïve individuals (rs2395029: [mean VL (copies/ml)], A/A: 70,795 [61,660-79,433], A/C: 33,884 [19,498-58,884], P=0.002; rs9264942: TT: 81,283 [67,608-97,724], T/C: 63,096 [54,954-75,858], CC: 38,905 [25,119-58,884], P<0.0001; rs3869068, CC: 72,444 [63,096-83,176], C/T: 45,709 [33,113-64,565], TT: 58,884 [20,417-169,824], P=0.01). Moreover, the C-alleles of rs2395029 and rs9264942 were associated with shorter time to VL<51 copies/ml: (HR [95% confidence interval], 1.67 [1.09-1.72], P=0.008; 1.16 [1.06-1.28], P=0.002; 1.30 [1.08-1.53], P=0.005, respectively, adjusted for last VL before cART). None of the SNPs predicted CD4(+) T-cell recovery during cART.CONCLUSIONS: The minor alleles of rs2395029, rs9264942, and rs3689068 associate with lower VL among antiretroviral-naïve individuals and with shorter time to first VL<51copies/ml during cART even after adjustment for VL before cART.

AB - AIMS: Single nucleotide polymorphisms (SNPs) in the human leucocyte antigen (HLA) complex P5 (HCP5), HLA-C, and near the zinc ribbon domain containing 1 (ZNRD1) have been shown to influence viral load (VL) set point in HIV-infected individuals with a known seroconversion onset. We aimed to determine the influence of HCP5 rs2395029, HLA-C rs9264942, and ZNRD1 rs3869068 on VL in antiretroviral-naïve individuals and on time to the first VL<51 copies/ml and on CD4(+) T-cell recovery after initiation of combination antiretroviral therapy (cART).MATERIAL AND METHODS: We genotyped the rs2395029 (A>C), rs9264942 (T>C), and rs3869068 (C>T) SNPs in 1897 Caucasians from The Danish HIV Cohort Study - a prospective, nationwide, population-based study of HIV-infected individuals in Denmark. General linear models evaluated the effect of SNPs on VL in antiretroviral-naïve individuals 0-18months after diagnosis and on CD4(+) T-cell recovery during cART. Cox proportional hazard regression analysis assessed the association with time to first VL<51 copies/ml. All models were assuming additive genetic effects.RESULTS: The rs2395029, rs9264942, and rs3869068 minor alleles were associated with lower VL in antiretroviral-naïve individuals (rs2395029: [mean VL (copies/ml)], A/A: 70,795 [61,660-79,433], A/C: 33,884 [19,498-58,884], P=0.002; rs9264942: TT: 81,283 [67,608-97,724], T/C: 63,096 [54,954-75,858], CC: 38,905 [25,119-58,884], P<0.0001; rs3869068, CC: 72,444 [63,096-83,176], C/T: 45,709 [33,113-64,565], TT: 58,884 [20,417-169,824], P=0.01). Moreover, the C-alleles of rs2395029 and rs9264942 were associated with shorter time to VL<51 copies/ml: (HR [95% confidence interval], 1.67 [1.09-1.72], P=0.008; 1.16 [1.06-1.28], P=0.002; 1.30 [1.08-1.53], P=0.005, respectively, adjusted for last VL before cART). None of the SNPs predicted CD4(+) T-cell recovery during cART.CONCLUSIONS: The minor alleles of rs2395029, rs9264942, and rs3689068 associate with lower VL among antiretroviral-naïve individuals and with shorter time to first VL<51copies/ml during cART even after adjustment for VL before cART.

KW - Journal Article

U2 - 10.1016/j.meegid.2016.03.037

DO - 10.1016/j.meegid.2016.03.037

M3 - Journal article

C2 - 27083073

VL - 41

SP - 185

EP - 190

JO - Infection, Genetics and Evolution

JF - Infection, Genetics and Evolution

SN - 1567-1348

ER -