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Impact of polymorphisms in the HCP5 and HLA-C, and ZRND1 genes on viral load.

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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,


Thørner LW, Erikstrup C, Harritshøj LH, Larsen MH, Kronborg G, Pedersen C, Larsen CS, Pedersen G, Gerstoft J, Obel N, Ullum H, (click to view)

Thørner LW, Erikstrup C, Harritshøj LH, Larsen MH, Kronborg G, Pedersen C, Larsen CS, Pedersen G, Gerstoft J, Obel N, Ullum H,

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Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 2016 4 12() pii 10.1016/j.meegid.2016.03.037

Abstract
AIMS
Single nucleotide polymorphisms (SNPs) in the HLA complex P5 gene (HCP5), HLA-C, and near the zinc ribbon domain containing 1 gene (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.

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