Association of polymorphisms of the mu opioid receptor gene with the severity of HIV infection and response to HIV treatment.

BACKGROUND Mu opioid receptor (OPRM1) ligands may alter expression of chemokines and chemokine receptors involved in penetration of human immunodeficiency virus (HIV) type 1 into the cell. We suggest that OPRM1 variants may affect the pathophysiology of HIV infection. METHODS DNA samples from 1031 eligible African Americans, Hispanics, and whites from the Women's Interagency HIV Study (WIHS) who were alive as of April 2006 were analyzed. We performed regression analysis of association of 18 OPRM1 variants with a change of viral load and CD4 cell count during 2 periods: between admission to WIHS and the start of highly active antiretroviral therapy (HAART) (interval X) and between the start of HAART and the most recent WIHS visit (interval Y), and examined the association of these variants with HIV status. RESULTS Regardless of genotype, a significant decrease in viral load during interval X was found for each ethnicity. Whites with allele G of the functional polymorphism 118A > G (reference sequence rs1799971) showed a smaller decrease in viral load; those bearing minor alleles IVS1 + 1050A, IVS1 + 14123A, and IVS2 + 31A showed a larger decrease in viral load over interval X (0.01 < P < .05). Hispanics with the same alleles showed a greater increase in CD4 cell count over interval Y (0.01 < P < .05). We found an association between OPRM1 variants and HIV status in African Americans and whites. CONCLUSIONS OPRM1 polymorphisms may alter the severity of HIV infection before and after HAART.

[1]  J. Varon,et al.  Mu‐opioid receptor A118G polymorphism in healthy volunteers affects hypothalamic–pituitary–adrenal axis adrenocorticotropic hormone stress response to metyrapone , 2013, Addiction biology.

[2]  K. Anastos,et al.  A C17T polymorphism in the mu opiate receptor is associated with quantitative measures of drug use in African American women , 2012, Addiction biology.

[3]  A. A. Palmer,et al.  OPRM1 gene variants modulate amphetamine‐induced euphoria in humans , 2011, Genes, brain, and behavior.

[4]  K. Shianna,et al.  Host determinants of HIV-1 control in African Americans. , 2010, The Journal of infectious diseases.

[5]  V. Yuferov,et al.  Drug-induced and genetic alterations in stress-responsive systems: Implications for specific addictive diseases , 2010, Brain Research.

[6]  T. Isowa,et al.  Association of polymorphism in the human μ-opioid receptor OPRM1 gene with proinflammatory cytokine levels and health perception , 2009, Brain, Behavior, and Immunity.

[7]  Mardge H. Cohen,et al.  CYP1A1 genotype modifies the impact of smoking on effectiveness of HAART among women. , 2009, AIDS education and prevention : official publication of the International Society for AIDS Education.

[8]  Harold McClure,et al.  Probable Deceleration of Progression of Simian AIDS Affected by Opiate Dependency: Studies With a Rhesus Macaque/SIVsmm9 Model , 2009, Journal of acquired immune deficiency syndromes.

[9]  Han Liu,et al.  The mechanism involved in the repression of the μ opioid receptor gene expression in CEM ×174 cells infected by simian immunodeficiency virus , 2009, Journal of leukocyte biology.

[10]  J. Rotrosen,et al.  Genetic susceptibility to heroin addiction: a candidate gene association study , 2008, Genes, brain, and behavior.

[11]  Mardge H. Cohen,et al.  Crack cocaine, disease progression, and mortality in a multicenter cohort of HIV-1 positive women , 2008, AIDS.

[12]  M. Kreek.  Role of a Functional Human Gene Polymorphism in Stress Responsivity and Addictions , 2008, Clinical pharmacology and therapeutics.

[13]  P. Sacerdote.  Opioid-induced immunosuppression , 2008, Current opinion in supportive and palliative care.

[14]  M. Kreek,et al.  The single nucleotide polymorphism A118G alters functional properties of the human mu opioid receptor , 2007, Journal of neurochemistry.

[15]  Yuying Xie,et al.  Effect of μ-Opioid Receptor Gene Polymorphisms on Heroin-Induced Subjective Responses in a Chinese Population , 2007, Biological Psychiatry.

[16]  Laforge Ks,et al.  Stress responsivity, addiction, and a functional variant of the human mu-opioid receptor gene. , 2007 .

[17]  M. Stein,et al.  Sexual risk behaviors among substance users: relationship to impulsivity. , 2006, Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors.

[18]  K. Kendler,et al.  The μ-opioid receptor gene and smoking initiation and nicotine dependence , 2006, Behavioral and Brain Functions.

[19]  M. Kreek,et al.  Altered Levels of Basal Cortisol in Healthy Subjects with a 118G Allele in Exon 1 of the Mu Opioid Receptor Gene , 2006, Neuropsychopharmacology.

[20]  Andrew D. Johnson,et al.  Allelic Expression Imbalance of Human mu Opioid Receptor (OPRM1) Caused by Variant A118G* , 2005, Journal of Biological Chemistry.

[21]  D. Vlahov,et al.  The relationship between non-injection drug use behaviors on progression to AIDS and death in a cohort of HIV seropositive women in the era of highly active antiretroviral therapy use. , 2005, Addiction.

[22]  M. Kreek,et al.  Pharmacogenetics and Human Molecular Genetics of Opiate and Cocaine Addictions and Their Treatments , 2005, Pharmacological Reviews.

[23]  J. Ott,et al.  Increased Attributable Risk Related to a Functional μ-Opioid Receptor Gene Polymorphism in Association with Alcohol Dependence in Central Sweden , 2005, Neuropsychopharmacology.

[24]  J. Ott,et al.  Substantial attributable risk related to a functional mu-opioid receptor gene polymorphism in association with heroin addiction in central Sweden , 2004, Molecular Psychiatry.

[25]  G. Rogers,et al.  Depressive disorders and unprotected casual anal sex among Australian homosexually active men in primary care , 2003, HIV medicine.

[26]  Hongyu Zhao,et al.  Haplotypes at the OPRM1 locus are associated with susceptibility to substance dependence in European‐Americans , 2003, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[27]  D. Oslin,et al.  A Functional Polymorphism of the μ-Opioid Receptor Gene is Associated with Naltrexone Response in Alcohol-Dependent Patients , 2003, Neuropsychopharmacology.

[28]  T. Rogers,et al.  μ-opioid modulation of HIV-1 coreceptor expressionand HIV-1 replication , 2003 .

[29]  P. Peterson,et al.  Opioid G protein-coupled receptors: signals at the crossroads of inflammation. , 2003, Trends in immunology.

[30]  M. Adler,et al.  Heterologous desensitization of opioid receptors by chemokines inhibits chemotaxis and enhances the perception of pain , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[31]  T. Rogers,et al.  Bidirectional Heterologous Desensitization of Opioid and Chemokine Receptors , 2000, Annals of the New York Academy of Sciences.

[32]  J J Goedert,et al.  Consistent associations of HLA class I and II and transporter gene products with progression of human immunodeficiency virus type 1 infection in homosexual men. , 1999, The Journal of infectious diseases.

[33]  R. Greenblatt,et al.  Sexual, contraceptive, and drug use behaviors of women with HIV and those at high risk for infection: results from the Women's Interagency HIV Study. , 1999, AIDS.

[34]  S. Leal,et al.  Single-nucleotide polymorphism in the human mu opioid receptor gene alters beta-endorphin binding and activity: possible implications for opiate addiction. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[35]  P. O’Connell,et al.  Genealogy of the CCR5 locus and chemokine system gene variants associated with altered rates of HIV-1 disease progression , 1998, Nature Medicine.

[36]  J J Goedert,et al.  Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression. Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC), ALIVE Study. , 1997, Science.

[37]  Steven M. Wolinsky,et al.  The role of a mutant CCR5 allele in HIV–1 transmission and disease progression , 1996, Nature Medicine.

[38]  J W Mulder,et al.  Virologic and immunologic benefits of initial combination therapy with zidovudine and zalcitabine or didanosine compared with zidovudine monotherapy. Wellcome Resistance Study Collaborative Group. , 1996, The Journal of infectious diseases.

[39]  J. Goedert,et al.  Influence of combinations of human major histocompatibility complex genes on the course of HIV–1 infection , 1996, Nature Medicine.

[40]  R. Gelber,et al.  Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. , 1994, The New England journal of medicine.

[41]  A. Abdul-Quader,et al.  Contrasting prevalence of delta hepatitis markers in parenteral drug abusers with and without AIDS. , 1990, The Journal of infectious diseases.

[42]  D. Vlahov,et al.  Cocaine injection and ethnicity in parenteral drug users during the early years of the human immunodeficiency virus (hiv) epidemic in new york city , 1989, Journal of medical virology.

[43]  Samuel R. Friedman,et al.  HIV-1 infection among intravenous drug users in Manhattan, New York City, from 1977 through 1987. , 1989, JAMA.

[44]  Chengyi Chang,et al.  Intron-mediated RNA interference, intronic microRNAs, and applications. , 2010, Methods in molecular biology.

[45]  M. Finley,et al.  Opioid and nociceptin receptors regulate cytokine and cytokine receptor expression. , 2008, Cellular immunology.

[46]  M. Kreek,et al.  Stress responsivity, addiction, and a functional variant of the human mu-opioid receptor gene. , 2007, Molecular interventions.

[47]  T. Rogers,et al.  Mu-opioid modulation of HIV-1 coreceptor expression and HIV-1 replication. , 2003, Virology.

[48]  D. Oslin,et al.  A functional polymorphism of the mu-opioid receptor gene is associated with naltrexone response in alcohol-dependent patients. , 2003, Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology.

[49]  R. Harrigan.  Measuring viral load in the clinical setting. , 1995, Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association.

[50]  M. Kreek,et al.  Antibody to LAV, the putative agent of AIDS, in parenteral drug abusers and methadone-maintained patients: therapeutic, historical, and ethical aspects. , 1986, NIDA research monograph.

[51]  L. Bierut,et al.  American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 144B:877–884 (2007) The Opioid System in Alcohol and Drug Dependence: Family-Based Association Study , 2022 .

[52]  Serveur Académique Lausannois SERVAL serval.unil.ch , 2022 .