title: Variations in the heme oxygenase-1 microsatellite polymorphism are associated with plasma CD14 and viral load in HIV-infected African-Americans.
abstract: Heme oxygenase-1 (HO-1) is an anti-inflammatory enzyme that maintains homeostasis during cellular stress. Given previous findings that shorter length variants of a HO-1 promoter region GT(n) microsatellite polymorphism are associated with increased HO-1 expression in cell lines, we hypothesized that shorter variants would also be associated with increased levels of HO-1 expression, less inflammation and lower levels of inflammation-associated viral replication in human immunodeficiency virus (HIV)-infected subjects. Healthy donors (n = 20) with shorter GT(n) repeats had higher HO-1 mRNA transcript in peripheral blood mononuclear cells stimulated with lipopolysaccharide (r = -0.38, P = 0.05). The presence of fewer GT(n) repeats in subjects with untreated HIV disease was associated with higher HO-1 mRNA levels in peripheral blood (r = -0.41, P = 0.02); similar observations were made in CD14(+) monocytes from antiretroviral-treated subjects (r = -0.36, P = 0.04). In African-Americans, but not Caucasians, greater GT(n) repeats were correlated with higher soluble CD14 levels during highly active antiretroviral therapy (r = 0.38, P = 0.007) as well as higher mean viral load off-therapy (r = 0.24, P = 0.04). These data demonstrate that the HO-1 GT(n) microsatellite polymorphism is associated with higher levels of HO-1 expression and that this pathway may have important effects on the association between inflammation and HIV replication.
authors: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94110, USA.
authors: L
authors: L
authors: Seu
authors: T D
authors: TD
authors: Burt
authors: J S
authors: JS
authors: Witte
authors: J N
authors: JN
authors: Martin
authors: S G
authors: SG
authors: Deeks
authors: J M
authors: JM
authors: McCune
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D001483:Base Sequence; D005260:Female; D015870:Gene Expression; D015658:HIV Infections / Q000208:ethnology / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D016130:Immunophenotyping; D018950:Lipopolysaccharide Receptors / Q000097:blood* / Q000378:metabolism; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D019562:Viral Load
chemical_list: D018950:Lipopolysaccharide Receptors; D051547:Heme Oxygenase-1