Genetic variation can have opposing effects on human disease, where the benefits of a protective variant against one disease can increase the risk of another. I provided four examples of the Yin/Yang of genetic variation in human health and disease:
CCR5Δ32: This variant protects against HIV-1, but associates with risk of symptomatic West Nile Virus infection.HLA-B*57: this is an HLA class I allele of the highly polymorphic HLA-B gene that confers protection against HIV-1, but associates with risk of psoriasis and abacavir hypersensitivity.HLA-C expression levels: complex variation outside of the protein coding region of the HLA-C gene determines HLA-C expression levels, where high expression associates with protection against HIV-1, but it also confers risk of Crohn’s Disease and graft vs. host disease after transplantation.Killer cell immunoglobulin-like receptors that confer activating states: These complex genotypes confer protection against KSHV infection, but among subjects with these genotypes who do become infected with KSHV, there is an increased risk of Kapok’s sarcoma.
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