Table 2.
GWAS significant genes associated with HIV-1 acquisition, viral load set point, and progression.
| Known gene | Description | Potential protein function | Effect | Population | Reference |
|---|---|---|---|---|---|
| HCP5 | HLA complex P5 | Related in sequence to human endogenous retroviruses and possibly interacts directly with HIV. | Minor alleles of SNPs rs2395029*, rs2255221, and rs2523608** were associated with low viral loads and delayed progression | Europeans, African Americans, and Africans | (Fellay et al., 2007; Dalmasso et al., 2008; Fellay et al., 2009; Limou et al., 2009; Pereyra et al., 2010; Le Clerc et al., 2011) |
| HLA-B | MHC class I B | Plays a critical role in the immune system; peptide presentation via endoplasmic reticulum (ER) pathway. | SNPs found in the gene were associated with low viral loads and delayed progression. | Europeans, Chinese, African Americans, and Africans | (Fellay et al., 2009; Herbeck et al., 2010; Pelak et al., 2010; Pereyra et al., 2010) |
| HLA-C | MHC class I C | Plays a critical role in the immune system; peptide presentation via endoplasmic reticulum (ER) pathway. | Minor allele of rs9264942 was associated with low viral loads and delayed progression. | Europeans | (Fellay et al., 2007; Fellay et al., 2009; Pereyra et al., 2010) |
| ZNRD1 | Zinc ribbon domain containing 1 | Plays a role in regulation of cell proliferation. | SNPs identified in this gene were associated with low viral loads and delayed progression. | Europeans | (Fellay et al., 2007, Fellay et al., 2009) |
| TNXB | Tenascin XB | Plays a role in matrix maturation during wound healing. | SNPs identified in this gene were associated with low viral loads. | Europeans | (Dalmasso et al., 2008) |
| TNF | Tumor necrosis factor | Cytokine. Involved in the regulation of biological processes including cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation. | Minor allele of SNP rs3093662 was associated with low viral loads. | Europeans | (Dalmasso et al., 2008) |
| SDC2 | Syndecan 2 | Mediates cell binding, cell signaling, and cytoskeletal organization. Syndecan receptors are required for internalization of the HIV-1 tat protein. | Minor allele of SNP rs2575735 was associated with reduction in HIV reservoir. | Europeans | (Dalmasso et al., 2008) |
| DDX40YPEL2 | DEAH-Box Helicase 40 Yippee Like 2 | NR | Minor allele of intergenic rs6503919 was associated with low viral reservoir. | Europeans | (Dalmasso et al., 2008) |
| TRIM10 | Tripartite motif containing 10 | Plays a role in terminal differentiation of erythroid cells. | SNP rs9468692 was associated with low viral loads. | Europeans | (Fellay et al., 2009) |
| NOTCH4 | Notch receptor 4 | Regulates interactions between physically adjacent cells. | Minor allele of SNP rs8192591 was associated with low viral loads and delayed progression. | Europeans | (Fellay et al., 2009; Le Clerc et al., 2011) |
| RNF39 | Ring finger protein 39 | Plays a role in early phase of synaptic plasticity. | SNPs found in the gene were associated with low viral loads and delayed progression. | Europeans | (Fellay et al., 2009; Limou et al., 2009) |
| C6orf48 | Small nucleolar RNA host gene 32 | NR | Minor allele of SNP rs9368699 was associated with low viral loads and delayed progression. | Europeans | (Limou et al., 2009; Le Clerc et al., 2011) |
| PSORS1C1 | Psoriasis susceptibility 1 candidate 1 | Confers susceptibility to psoriasis and systemic sclerosis. | SNPs found in the gene were associated with low viral loads. | Europeans | (Limou et al., 2009) |
| MICB | MHC class I polypeptide-related sequence B | Involved in immune response. Activates natural killer cells, CD8 alphabeta T cells, and gammadelta T cells. | SNPs found in the gene were associated with low viral loads. | Europeans | (Limou et al., 2009; Herbeck et al., 2010) |
| SOX5 | Sex determining region Y -box 5 | Regulation of embryonic development and determination of the cell fate. | Minor allele of SNP rs1522232 was associated with delayed progression. | Europeans | (Le Clerc et al., 2009) |
| RXRG | Retinoid X receptor gamma | Mediates the antiproliferative effects of retinoic acid. | Minor allele of SNP rs10800098 was associated with rapid progression. | Europeans | (Le Clerc et al., 2009) |
| TGFBRAP1 | Transforming growth factor beta receptor associated protein 1 | Acts as a chaperone in signaling downstream of TGF-beta. | Minor allele of SNP rs1020064 was associated with delayed progression. | Europeans | (Le Clerc et al., 2009) |
| PROX1 | Prospero homeobox 1 | Plays a role in development. | A haplotype of rs17762192, rs17762150, and rs1367951 was associated with delayed progression. | Europeans | (Herbeck et al., 2010) |
| MICA | MHC class I polypeptide-related sequence A | A ligand for the NKG2-D type II receptor that acts as a stress-induced antigen that is broadly recognized by intestinal epithelial gamma delta T cells. | Minor allele of SNP rs4418214 was associated with low viral loads. | Europeans | (Pereyra et al., 2010) |
| PSORS1C3 | Psoriasis susceptibility 1 candidate 3 | NR | Minor allele of SNP rs3131018 was associated with low viral loads. | Europeans | (Pereyra et al., 2010) |
| AL671883.2 DHFRP2 | Pseudogenes | NR | Minor allele of intergenic SNP rs2523590 was associated with low viral loads. | Europeans, African Americans, Hispanics | (Pereyra et al., 2010) |
| HCG22 | HLA complex group 22 | NR | Minor allele of SNP rs9262632 was associated with low viral loads in African Americans. Minor allele of SNP rs2535307 was associated with rapid progression and increased susceptibility. | African Americans and Southern Africans | (Pereyra et al., 2010; Xie et al., 2017) |
| RICH2 | Rho GTPase activating protein 44 | Involved in GTPase activation activity and phospholipid binding. | Major allele of SNP rs2072255 was associated with rapid progression. | Europeans | (Le Clerc et al., 2011) |
| PARD3B | Par-3 family cell polarity regulator beta | May play a role in asymmetrical cell division and cell polarization processes. | SNP rs11884476 was associated with delayed progression. | Europeans | (Troyer et al., 2011) |
| CCR5 | C-C motif chemokine receptor 5 | Acts as a co-receptor for macrophage-tropic viruses to enter host cells. | CCR5-Δ32 was associated with resistance to HIV-1 infection. | Europeans | (McLaren et al., 2013) |
| CCNG1 | Cyclin G1 | May play a role in cell proliferation and regulation | SNP kgp22385164 was associated with rapid progression. | Southern Africans | (Xie et al., 2017) |
Potential function of genes according to Pubmed and GeneCards. MHC, major histocompatibility complex; SNP, single nucleotide polymorphism; *, SNP tags HLA-B57*01 in Europeans; **, SNP tags HLA-B57*03 in Africans; NR, no records.