Document Detail


Polymorphisms of the kappa opioid receptor and prodynorphin genes: HIV risk and HIV natural history.
MedLine Citation:
PMID:  23392455     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Studies indicate cross-desensitization between opioid receptors (eg, kappa opioid receptor, OPRK1) and chemokine receptors (eg, CXCR4) involved in HIV infection. Whether gene variants of OPRK1 and its ligand, prodynorphin (PDYN), influence the outcome of HIV therapy was tested.
METHODS: Three study points, admission to the Women's Interagency HIV Study, initiation of highly active antiretroviral therapy (HAART), and the most recent visit, were chosen for analysis as crucial events in the clinical history of the HIV patients. Regression analyses of 17 variants of OPRK1 and 11 variants of PDYN with change of viral load (VL) and CD4 count between admission and initiation of HAART and initiation of HAART to the most recent visit to Women's Interagency HIV Study were performed in 598 HIV+ subjects, including African Americans, Hispanics, and Whites. Association with HIV status was done in 1009 subjects.
RESULTS: Before HAART, greater VL decline (improvement) in carriers of PDYN IVS3+189C>T and greater increase of CD4 count (improvement) in carriers of OPRK -72C>T were found in African Americans. Also, greater increase of CD4 count in carriers of OPRK1 IVS2+7886A>G and greater decline of CD4 count (deterioration) in carriers of OPRK1 -1205G>A were found in Whites. After HAART, greater decline of VL in carriers of OPRK1 IVS2+2225G>A and greater increase of VL in carriers of OPRK1 IVS2+10658G>T and IVS2+10963A>G were found in Whites. Also, a lesser increase of CD4 count was found in Hispanic carriers of OPRK1 IVS2+2225G>A.
CONCLUSIONS: OPRK1 and PDYN polymorphisms may alter severity of HIV infection and response to treatment.
Authors:
Dmitri Proudnikov; Matthew Randesi; Orna Levran; Vadim Yuferov; Howard Crystal; Ann Ho; Jurg Ott; Mary J Kreek
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of acquired immune deficiency syndromes (1999)     Volume:  63     ISSN:  1944-7884     ISO Abbreviation:  J. Acquir. Immune Defic. Syndr.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-11     Completed Date:  2013-06-24     Revised Date:  2014-10-22    
Medline Journal Info:
Nlm Unique ID:  100892005     Medline TA:  J Acquir Immune Defic Syndr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17-26     Citation Subset:  IM; X    
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MeSH Terms
Descriptor/Qualifier:
African Americans / genetics
Antiretroviral Therapy, Highly Active
CD4 Lymphocyte Count
European Continental Ancestry Group / genetics
HIV Infections / drug therapy,  genetics*,  physiopathology*,  virology
HIV-1 / pathogenicity
Hispanic Americans / genetics
Humans
Polymorphism, Single Nucleotide / genetics*
Prognosis
Receptors, CXCR4 / genetics*
Receptors, Opioid, kappa / genetics*
Risk Factors
Treatment Outcome
Viral Load
Grant Support
ID/Acronym/Agency:
AI-35004/AI/NIAID NIH HHS; MH79880/MH/NIMH NIH HHS; P60 DA005130/DA/NIDA NIH HHS; P60-DA05130/DA/NIDA NIH HHS; R01 MH076537/MH/NIMH NIH HHS; R01 MH079880/MH/NIMH NIH HHS; UL1 RR024131/RR/NCRR NIH HHS; UO1-AI-31834/AI/NIAID NIH HHS; UO1-AI-34989/AI/NIAID NIH HHS; UO1-AI-34993/AI/NIAID NIH HHS; UO1-AI-34994/AI/NIAID NIH HHS; UO1-AI-42590/AI/NIAID NIH HHS; UO1-HD-32632/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/CXCR4 protein, human; 0/OPRK1 protein, human; 0/Receptors, CXCR4; 0/Receptors, Opioid, kappa
Comments/Corrections

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