title: YWHAE/14-3-3ε: a potential novel genetic risk factor and CSF biomarker for HIV neurocognitive impairment.
abstract: YWHAE (14-3-3ε) protein levels are considered to be a reliable biomarker for neurodegeneration. The YWHAE protein interacts both directly and indirectly with human immunodeficiency virus (HIV) accessory proteins, leading to cell death. The purpose of this study was to examine the relationship between YWHAE polymorphisms and HIV-associated neurocognitive disorder (HAND) and the relationship between YWHAE protein levels and HAND. A cross-sectional study using random samples of HIV-seropositive (n = 20) and HIV-seronegative (controls) (n = 16) women from the Hispanic-Latino Longitudinal Cohort of Women was conducted. Individuals who are HIV-seropositive and heterozygous at the rs4790084/rs1204828 loci in the YWHAE gene were 3× more likely to display reduced cognitive functioning, to have received a HAND diagnosis, and to have less YHWAE protein expressed than homozygotes. Western blots from cerebral spinal fluid indicate that the HIV-seropositive women with HAND expressed 4.5× less YWHAE compared to HIV-seropositive cognitively normal women (94 % sensitivity, 84 % specificity; HIV-seropositive vs. controls). Therefore, polymorphism in YWHAE may be a genetic risk factor for HAND and levels of YWHAE protein are a likely biomarker for neurocognitive status in HIV-seropositive women.
authors: Department of Physiology, Pharmacology, and Toxicology, Ponce School of Medicine and Health Sciences, Ponce, Puerto Rico.
authors: Diana
authors: D
authors: Morales
authors: Rosa
authors: R
authors: Hechavarria
authors: Valerie
authors: V
authors: Wojna
authors: Summer F
authors: SF
authors: Acevedo
mesh_terms: D048948:14-3-3 Proteins / Q000134:cerebrospinal fluid / Q000235:genetics*; D000328:Adult; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D003430:Cross-Sectional Studies; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006678:HIV; D015658:HIV Infections / Q000150:complications / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D018023:HIV Seronegativity; D006679:HIV Seropositivity; D006579:Heterozygote; D006630:Hispanic or Latino; D006720:Homozygote; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D048948:14-3-3 Proteins; C482983:YWHAE protein, human
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