Dataset Information

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

ABSTRACT: 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-?-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.

SUBMITTER: Blumenthal MJ

PROVIDER: S-EPMC6206435 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Blumenthal Melissa J MJ Schutz Charlotte C Meintjes Graeme G Mohamed Zainab Z Mendelson Marc M Ambler Jon M JM Whitby Denise D Mackelprang Romel D RD Carse Sinead S Katz Arieh A AA Schäfer Georgia G

Cancer epidemiology 20180831

<h4>Background</h4>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.<h4>Methods</h4>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<sup>+</sup>/KSHV<sup>+</sup>; group 2: KS<sup>-</sup>/KSHV ...[more]

PMID: 30176543

Similar Datasets

Project description:MicroRNAs (miRNAs) are the non-coding RNAs that can both attach to the untranslated and coding sections of target mRNAs, triggering destruction or post-transcriptional alteration. miRNAs regulate various cellular processes such as immune function, apoptosis, and tumorigenesis. About 35,000 miRNAs have been discovered in the human genome. The increasing evidence suggests that the dysregulation of human miRNAs may have a role in the etiology of some disorders including cancer. Only a small sub-set of human miRNAs has functionally been validated in the pathogenesis of oncogenic viruses such as Kaposi's sarcoma-associated herpesvirus (KSHV). KSHV is the cause of various human malignancies including primary effusion lymphoma (PEL) and Kaposi's sarcoma (KS), which are mainly seen in AIDS patients or other immunocompromised people. We aimed to identify the miRNAs in Kaposi's sarcoma cases, with the comparison of KSHV seropositive and seronegative tumors with the controls and in each other in Turkish Kaposi's sarcoma patients. We performed the miRNA-sequencing at genome level in the peripheral blood mononuclear cells of 16 Kaposi's sarcoma patients, and in 8 healthy controls matched for age, gender, and ethnicity. A total of 642 miRNA molecules with different expression profiles were identified between the patients and the healthy controls. Currently, out of 642 miRNAs, 7 miRNAs (miR-92b-3p, miR-490-3p, miR-615-3p, miR-629-5p, miR-1908, miR-3180, miR-4433b-3p) which have not been described in the literature in the context of Kaposi's sarcoma were addressed in the study for the first time and 9 novel miRNAs, not found previously in the database, have been detected in Kaposi's sarcoma using the miRNA-sequencing technique. This study demonstrates the identification of differently expressed miRNAs which might be the new therapeutic targets for Kaposi's sarcoma, that has limited treatment options and can be used in the etiology, diagnosis, and prognosis of this cancer.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets