Elsevier

Human Immunology

Volume 78, Issue 2, February 2017, Pages 179-184
Human Immunology

Psoriasis risk SNPs and their association with HIV-1 control

https://doi.org/10.1016/j.humimm.2016.10.018Get rights and content

Abstract

Human evolution has resulted in selection for genetic polymorphisms beneficial in the defense against pathogens. However, such polymorphisms may have the potential to heighten the risk of autoimmune disease. Here, we investigated whether psoriasis-associated single nucleotide polymorphisms influence host control of HIV-1 infection. We studied psoriasis and viral immune response variants in three HIV-positive cohorts: (1) HIV-1 controllers and non-controllers in the Study of the Consequences of the Protease Inhibitor Era (SCOPE) cohort (n = 366), (2) Individuals with primary HIV infection in the Options cohort (n = 675), and (3) HIV-positive injection drug users from the Urban Health Study (UHS) (n = 987). We found a strong association of two psoriasis MHC variants, rs9264942 and rs3021366, with both HIV-1 controller status and viral load, and identified another Class III MHC variant rs9368699 to be strongly associated with viral load. A number of genetic variants outside the MHC (SOX5, TLR9, SDC4, PROX1, IL12B, TLR4, MBL-2, TYK2, IFIH1) demonstrated nominal significance. Overall, our data suggest that several psoriasis variants within the MHC have a robust impact on HIV-1 control, while variants outside the MHC require further investigation.

Introduction

Psoriasis is an immune-mediated inflammatory condition where the excessive immune activation results in inflammation of the skin and raised red scaly patches. Psoriasis has a worldwide prevalence of 2–4% [1]. Previous segregation and linkage analysis show psoriasis to be a heritable condition as evidenced by a twin concordance rate of 70% and a sibling recurrence risk λs between 4–11 [2].

HIV-1 control is a rare immunologic phenotype in approximately 1% of HIV-1 infected individuals in which patients who are infected with the HIV-1 virus spontaneously maintain low viral loads in the absence of anti-retroviral therapy (ART). HIV-1 control has been observed across all ethnicities and modes of viral transmission and it has been shown to be associated with certain genetic and immunologic characteristics [3].

Our previous work analyzing genetic variants in the major histocompatibility (MHC) region in psoriasis cases versus controls revealed that psoriasis patients are enriched for several human leukocyte antigen (HLA) class I alleles that are also associated with HIV-1 control [4]. A follow-up study demonstrated that there is a significant increase in antiviral gene expression in psoriasis lesional skin compared to healthy controls [5]. Another study showed that HLA-C alleles associated with higher HLA-C surface expression contribute to viral control in HIV but lead to an increase in risk of another immune-mediated disease, Crohn’s disease [6]. Together, these studies suggest that some genetic variants that protect the human host against viral pathogens may also increase the risk of autoimmune disease.

Here, to further understand the genetic relationship between psoriasis and HIV-1 control, we genotyped a more comprehensive panel of psoriasis risk single nucleotide polymorphisms (SNPs) in HIV cohorts to determine if viral control is associated with psoriasis susceptibility SNPs. We also genotyped a number of known viral control SNPs to evaluate whether they were associated with HIV-1 control.

Section snippets

Subjects

Three HIV cohorts were examined in this study: Study of the Consequences of the Protease Inhibitor Era (SCOPE) and Options as discovery cohorts and the Urban Health Study (UHS) as a replication cohort.

The SCOPE cohort is an ongoing prospective cohort study at the University of California San Francisco (UCSF) where HIV-positive participants are seen at 4-month intervals to complete questionnaires and provide a blood sample to determine HIV plasma RNA level and CD4+ T cell count. A subset of

Results

We evaluated 43 psoriasis risk SNPs, 39 viral control SNPs and 2 SNPs associated with both psoriasis and viral control in the SCOPE and Options cohort and then tested the top SNPs in the UHS dataset for replication.

In the Caucasian population of SCOPE, the SNPs passing the Bonferroni correction (p-value less than 0.000658) were rs9264942, which is 35 kb upstream from HLA-C (OR = 2.61, p = 0.00062), and rs3021366 which tags the HLA-B * 5701 allele (OR = 5.99, p = 0.000497) as shown in Table 2. For both of

Discussion

In this study, we investigated a set of psoriasis risk SNPs and viral control SNPs in HIV cohorts to examine whether these SNPs influence HIV-1 control or viral load. We observed two strong hits in the MHC class I region. The rs3021366 SNP tagging the HLA-B * 5701 allele had a strong effect in the SCOPE, Options, and UHS cohorts which affirms previous findings that the HLA-B * 5701 allele is protective in HIV-1 disease[13][14][15]. The HLA-B * 5701 allele has also been strongly associated with

Acknowledgements

W.L. is supported by grants from the NIH (R01AR065174, U01AI119125). Further funding was from the Creative and Novel Ideas in HIV Research Program (CNIHR) through a supplement to the University of Alabama at Birmingham (UAB) Center For AIDS Research funding (P30 AI027767-24), made possible by collaborative efforts of the Office of AIDS Research, the National Institutes of Allergies and Infectious Diseases, and the International AIDS Society. S.D. is supported by the UCSF/Gladstone Institute of

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