EPHA2 sequence variants are associated with susceptibility to Kaposi's sarcoma-associated herpesvirus infection and Kaposi's sarcoma prevalence in HIV-infected patients.

Autor: Blumenthal MJ; Division of Medical Biochemistry and Structural Biology, Department of Integrative Biomedical Sciences, University of Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa., Schutz C; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa; Wellcome Centre for Infectious Diseases Research in Africa, University of Cape Town, South Africa., Meintjes G; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa; Wellcome Centre for Infectious Diseases Research in Africa, University of Cape Town, South Africa., Mohamed Z; Division of Radiation Oncology, Department of Radiation Medicine, University of Cape Town, South Africa., Mendelson M; Division of Infectious Diseases & HIV Medicine, Department of Medicine, University of Cape Town, South Africa., Ambler JM; Computational Biology Group, Department of Integrative Biomedical Sciences, University of Cape Town, South Africa., Whitby D; Viral Oncology Section, AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, NIH, USA., Mackelprang RD; University of Washington, USA., Carse S; Division of Medical Biochemistry and Structural Biology, Department of Integrative Biomedical Sciences, University of Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa., Katz AA; Division of Medical Biochemistry and Structural Biology, Department of Integrative Biomedical Sciences, University of Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa., Schäfer G; Division of Medical Biochemistry and Structural Biology, Department of Integrative Biomedical Sciences, University of Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa. Electronic address: georgia.schafer@uct.ac.za.
Jazyk: angličtina
Zdroj: Cancer epidemiology [Cancer Epidemiol] 2018 Oct; Vol. 56, pp. 133-139. Date of Electronic Publication: 2018 Aug 31.
DOI: 10.1016/j.canep.2018.08.005
Abstrakt: Background: To determine if variations exist in the KSHV host receptor EPHA2's coding region that affect KSHV infectivity and/or KS prevalence among South African HIV-infected patients.
Methods: A retrospective candidate gene association study was performed on 150 patients which were randomly selected from a total of 756 HIV-infected patients and grouped according to their KS status and KSHV serodiagnosis; namely group 1: KS + /KSHV + ; group 2: KS - /KSHV + ; group 3: KS - /KSHV - . Peripheral blood DNA was used to extract DNA and PCR amplify and sequence the entire EPHA2 coding region, which was compared to the NCBI reference through multiple alignment.
Results: 100% (95% CI 92.9-100%) of the KS positive patients, and 31.6% (95% CI 28.3-35.1%) of the KS negative patients were found to be KSHV seropositive. Aggregate variation across the entire EPHA2 coding region identified an association with KS (OR = 6.6 (95% CI 2.8, 15.9), p = 2.2 × 10 -5 ). This was primarily driven by variation in the functionally important protein tyrosine kinase domain (Pkinase-Tyr; OR = 4.9 (95% CI 1.9, 12.4), p = 0.001) and the sterile-α-motif (SAM; OR = 13.8 (95% CI 1.7, 111.6), p = 0.014). Mutation analysis revealed two novel, non-synonymous heterozygous variants (c.2254 T > C: OR undefined, adj. p = 0.02; and c.2990 G > T: OR undefined, adj. p = 0.04) in Pkinase-Tyr and SAM, respectively, to be statistically associated with KS; and a novel heterozygous transition (c.2727C > T: OR = 6.4 (95% CI 1.4, 28.4), adj. p = 0.03) in Pkinase-Tyr to be statistically associated with KSHV.
Conclusions: Variations in the KSHV entry receptor gene EPHA2 affected susceptibility to KSHV infection and KS development in a South African HIV-infected patient cohort.
(Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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