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Phenotypic expressions of CCR5-Delta 32/Delta 32 homozygosity

  1. Author:
    Nguyen, G. T.
    Carrington, M.
    Beeler, J. A.
    Dean, M.
    Aledort, L. M.
    Blatt, P. M.
    Cohen, A. R.
    DiMichele, D.
    Eyster, M. E.
    Kessler, C. M.
    Konkle, B.
    Leissinger, C.
    Luban, N.
    O'Brien, S. J.
    Goedert, J. J.
    O'Brien, T. R.

  2. Author Address

    O'Brien TR US Dept HHS, Viral Epidemiol Branch, NCI 6120 Execut Blvd 8016 Rockville, MD 20852 USA US Dept HHS, Viral Epidemiol Branch, NCI Rockville, MD 20852 USA NIH, Howard Hughes Med Inst, Res Scholars Program Bethesda, MD 20892 USA NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick Frederick, MD USA US FDA, Div Viral Prod Bethesda, MD 20014 USA NCI, Lab Genomic Divers Frederick, MD 21701 USA Mt Sinai Med Ctr, Hemophilia Ctr New York, NY 10029 USA Christiana Hosp, Delaware Clin & Lab Phys Newark, DE USA Childrens Hosp Philadelphia, Hemophilia Ctr, Dept Hematol Philadelphia, PA 19104 USA Cornell Univ, Med Ctr, New York Hosp, Dept Pediat Hematol Oncol New York, NY 10021 USA Penn State Univ, Milton S Hershey Med Ctr, Sch Med, Div Hematol Oncol Hershey, PA 17033 USA Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr Washington, DC 20007 USA Thomas Jefferson Univ Hosp, Cardeza Fdn Hemophilia Ctr Philadelphia, PA 19107 USA Tulane Univ, Sch Med, Hematol Oncol Sect New Orleans, LA 70112 USA Childrens Hosp, Natl Med Ctr, Dept Hematol Oncol, Hemophilia Ctr Washington, DC 20010 USA
    1. Year: 1999
  2. Journal: Jaids-Journal of Acquired Immune Deficiency Syndromes
    1. 22
    2. 1
    3. Pages: 75-82
  4. Type of Article: Article
  1. Abstract:

    Objective: As blockade of CC-chemokine receptor 5 (CCR5) has been proposed as therapy for HIV-1, we examined whether the CCR5-Delta 32/Delta 32 homozygous genotype has phenotypic expressions other than those related to HIV-1. Design: Study subjects were white homosexual men or men with hemophilia who were not infected with HIV-1. In this study, 15 CCR5-Delta 32/Delta 32 homozygotes were compared with 201 CCR5 wild-type (+/+) subjects for a wide range of clinical conditions and laboratory assay results ascertained during prospective cohort studies and routine clinical care. CCR5-Delta 32 genotype was determined by polymerase chain reaction, followed by single-stranded conformational polymorphism analysis. Results: Hypertension and conditions attributable to hemophilia were the only diagnoses frequently found in clinical records of CCR5-Delta 32/Delta 32 study subjects. Based on blood pressure measurement and treatment history, CCR5-Delta 32/Delta 32 homozygotes had a 2.8-fold higher prevalence of hypertension than age-matched CCR5-+/+ study subjects (95% confidence interval [CI], 1.2-6.4; p = .01); none of the homozygotes had severe hypertension. Hematologic measures were generally similar across the genotypes, but total lymphocyte counts were similar to 20% higher in CCR5-Delta 32/Delta 32 study subjects than in CCR5-+/+ study subjects (p < .05). Among patients with hemophilia who were infected with hepatitis C virus (HCV), mean alanine aminotransferase levels were 117% higher among CCR5-Delta 32/Delta 32 homozygotes (p < .05), but serum HCV levels did not differ by CCR5-Delta 32 genotype. CCR5-Delta 32/Delta 32 homozygous study subjects had a lower prevalence of antibodies to measles virus than those with other genotypes, but this association was not confirmed in a group of blood donors. The prevalence of antibodies to nine other common viruses, HBV, and HCV was not related to CCR5 genotype. Conclusions: CCR5-Delta 32/Delta 32 homozygotes are generally similar to wild-type persons. Confirmatory investigations are required to determine whether hypertension, increased lymphocyte counts, and higher hepatic enzyme levels in the presence of HCV infection represent true phenotypic expressions of this genotype. CCR5-Delta 32/Delta 32 homozygosity does not provide broad protection against viral infections. [References: 39]

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