title: Psoriasis patients are enriched for genetic variants that protect against HIV-1 disease.
abstract: An important paradigm in evolutionary genetics is that of a delicate balance between genetic variants that favorably boost host control of infection but which may unfavorably increase susceptibility to autoimmune disease. Here, we investigated whether patients with psoriasis, a common immune-mediated disease of the skin, are enriched for genetic variants that limit the ability of HIV-1 virus to replicate after infection. We analyzed the HLA class I and class II alleles of 1,727 Caucasian psoriasis cases and 3,581 controls and found that psoriasis patients are significantly more likely than controls to have gene variants that are protective against HIV-1 disease. This includes several HLA class I alleles associated with HIV-1 control; amino acid residues at HLA-B positions 67, 70, and 97 that mediate HIV-1 peptide binding; and the deletion polymorphism rs67384697 associated with high surface expression of HLA-C. We also found that the compound genotype KIR3DS1 plus HLA-B Bw4-80I, which respectively encode a natural killer cell activating receptor and its putative ligand, significantly increased psoriasis susceptibility. This compound genotype has also been associated with delay of progression to AIDS. Together, our results suggest that genetic variants that contribute to anti-viral immunity may predispose to the development of psoriasis.
authors.affiliation: Department of Dermatology, University of California San Francisco, San Francisco, California, USA.
authors.forename: Haoyan
authors.initials: H
authors.lastname: Chen
authors.forename: Genki
authors.initials: G
authors.lastname: Hayashi
authors.forename: Olivia Y
authors.initials: OY
authors.lastname: Lai
authors.forename: Alexander
authors.initials: A
authors.lastname: Dilthey
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Kuebler
authors.forename: Tami V
authors.initials: TV
authors.lastname: Wong
authors.forename: Maureen P
authors.initials: MP
authors.lastname: Martin
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Fernandez Vina
authors.forename: Gil
authors.initials: G
authors.lastname: McVean
authors.forename: Matthias
authors.initials: M
authors.lastname: Wabl
authors.forename: Kieron S
authors.initials: KS
authors.lastname: Leslie
authors.forename: Toby
authors.initials: T
authors.lastname: Maurer
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Martin
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
authors.forename: Anne M
authors.initials: AM
authors.lastname: Bowcock
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Nixon
authors.forename: Wilson
authors.initials: W
authors.lastname: Liao
mesh_terms: D005805:Genes, MHC Class I / Q000276:immunology; D005802:Genes, MHC Class II / Q000276:immunology; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity; D015235:HLA-B Antigens / Q000235:genetics; D015236:HLA-C Antigens / Q000235:genetics; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism / Q000821:virology; D011110:Polymorphism, Genetic; D011485:Protein Binding; D011565:Psoriasis / Q000235:genetics* / Q000276:immunology*; D054349:Receptors, KIR3DS1 / Q000235:genetics
chemical_list: D015235:HLA-B Antigens; D015236:HLA-C Antigens; D054349:Receptors, KIR3DS1