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Background  Most of the circulating Vitamin D (VitD) is transported bound to vitamin D-binding protein (DBP), and several DBP single nucleotide polymorphisms (SNPs) have been related to circulating VitD concentration and disease. In this study, we evaluated the association among  DBP  SNPs and AIDS progression in antiretroviral treatment (ART)-naïve-HIV-infected patients.    Methods  We performed a retrospective study in 667 patients who were classified according to their pattern of AIDS progression (183 long-term non-progressors (LTNPs), 334 moderate progressors (MPs), and 150 rapid progressors (RPs)) and 113 healthy blood donors (HIV, HCV, and HBV negative subjects). We genotyped seven  DBP  SNPs (rs16846876, rs12512631, rs2070741, rs2282679, rs7041, rs1155563, rs2298849) using Agena Bioscience’s MassARRAY platform. The genetic association was evaluated by Generalized Linear Models adjusted by age at the moment of HIV diagnosis, gender, risk group, and  VDR  rs2228570 SNP. Multiple testing correction was performed by the false discovery rate (Benjamini and Hochberg procedure; q-value).    Results  All SNPs were in HWE ( p  > 0.05) and had similar genotypic frequencies for  DBP  SNPs in healthy-controls and HIV-infected patients. In unadjusted GLMs, we only found significant association with AIDS progression in rs16846876 and rs12512631 SNPs. In adjusted GLMs,  DBP  rs16846876 SNP showed significant association under the recessive inheritance model [LTNPs vs. RPs (adjusted odds ratio (aOR) = 3.53;  q -value = 0.044) and LTNPs vs. MPs (aOR = 3.28;  q -value = 0.030)] and codominant [LTNPs vs. RPs (aOR = 4.92;  q -value = 0.030) and LTNPs vs. MPs (aOR = 3.15;  q -value = 0.030)]. Also, we found  DBP  rs12512631 SNP showed significant association in the inheritance model dominant [LTNPs vs. RPs (aOR = 0.49;  q -value = 0.031) and LTNPs vs. MPs (aOR = 0.6;  q -value = 0.047)], additive [LTNPs vs. RPs (aOR = 0.61;  q -value = 0.031)], overdominant [LTNPs vs. MPs (aOR = 0.55;  q -value = 0.032)], and codominant [LTNPs vs. RPs (aOR = 0.52;  q -value = 0.036) and LTNPs vs. MPs (aOR = 0.55;  q -value = 0.032)]. Additionally, we found a significant association between  DBP  haplotypes (composed by rs16846876 and rs12512631) and AIDS progression (LTNPs vs RPs):  DBP  haplotype AC (aOR = 0.63;  q -value = 0.028) and the  DBP  haplotype TT (aOR = 1.64;  q -value = 0.028).    Conclusions   DBP  rs16846876 and rs12512631 SNPs are related to the patterns of clinical AIDS progression (LTNP, MP, and RP) in ART-naïve HIV-infected patients. Our findings provide new knowledge about AIDS progression that may be relevant to understanding the pathogenesis of HIV infection.

DBP rs16846876 and rs12512631 polymorphisms are associated with progression to AIDS naïve HIV-infected patients: a retrospective study