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

doi:10.1016/j.meegid.2016.03.037

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

Institut for Klinisk Medicin

5 Citationer (Scopus)

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 0-18 months 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 < 51 copies/ml during cART even after adjustment for VL before cART.

Originalsprog	Engelsk
Tidsskrift	Infection, Genetics and Evolution
Vol/bind	41
Sider (fra-til)	185-190
Antal sider	6
ISSN	1567-1348
DOI	https://doi.org/10.1016/j.meegid.2016.03.037
Status	Udgivet - 1 jul. 2016

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10.1016/j.meegid.2016.03.037

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@article{24733d21bd994790917d5fc69be11371,

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 0-18 months 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 < 51 copies/ml during cART even after adjustment for VL before cART.",

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",

year = "2016",

month = jul,

day = "1",

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",

}

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

PY - 2016/7/1

Y1 - 2016/7/1

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 0-18 months 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 < 51 copies/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 0-18 months 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 < 51 copies/ml during cART even after adjustment for VL before cART.

U2 - 10.1016/j.meegid.2016.03.037

DO - 10.1016/j.meegid.2016.03.037

M3 - Journal article

C2 - 27083073

SN - 1567-1348

VL - 41

SP - 185

EP - 190

JO - Infection, Genetics and Evolution

JF - Infection, Genetics and Evolution

ER -

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

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