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