Repeat-region polymorphisms in the gene for the dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin-related molecule: effects on HIV-1 susceptibility.

In 1716 individuals--801 human immunodeficiency virus (HIV)-1-seropositive individuals, 217 high-risk HIV-1-seronegative individuals, and 698 general HIV-1-seronegative individuals--from a Seattle cohort and a Multicenter AIDS Cohort Study cohort, the association between HIV-1 susceptibility and repeat-region polymorphisms in the gene for the dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin-related molecule (DC-SIGNR) was investigated; 16 genotypes were found in the DC-SIGNR repeat region. The DC-SIGNR homozygous 7/7 repeat was found to be associated with an increased risk of HIV-1 infection (17.5% in high-risk HIV-1-seronegative individuals vs. 28.5% in HIV-1-seropositive individuals; P=.0015), whereas the DC-SIGNR heterozygous 7/5 repeat tended to be correlated with resistance to HIV-1 infection (35.5% in high-risk HIV-1-seronegative individuals vs. 27.6% in HIV-1-seropositive individuals; P=.0291). These findings suggest that DC-SIGNR polymorphisms may influence susceptibility to HIV-1.

[1]  M. McElrath,et al.  Most DC-SIGNR transcripts at mucosal HIV transmission sites are alternatively spliced isoforms , 2005, European Journal of Human Genetics.

[2]  M. McElrath,et al.  Analysis of genetic polymorphisms in CCR5, CCR2, stromal cell-derived factor-1, RANTES, and dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin in seronegative individuals repeatedly exposed to HIV-1. , 2004, The Journal of infectious diseases.

[3]  J. Lang,et al.  Most Highly Exposed Seronegative Men Lack HIV-1-Specific, IFN-γ-Secreting T Cells 1 , 2003, The Journal of Immunology.

[4]  M. Carrington,et al.  Association of polymorphisms in human leukocyte antigen class I and transporter associated with antigen processing genes with resistance to human immunodeficiency virus type 1 infection. , 2003, The Journal of infectious diseases.

[5]  J. van Lunzen,et al.  The tandem-repeat polymorphism of the DC-SIGNR gene does not affect the susceptibility to HIV infection and the progression to AIDS. , 2003, Clinical immunology.

[6]  W. Sugiura,et al.  Polymorphisms and haplotypes of the CD209L gene and their association with the clinical courses of HIV-positive Japanese patients. , 2002, Japanese journal of infectious diseases.

[7]  S. Mummidi,et al.  Extensive Repertoire of Membrane-bound and Soluble Dendritic Cell-specific ICAM-3-grabbing Nonintegrin 1 (DC-SIGN1) and DC-SIGN2 Isoforms , 2001, The Journal of Biological Chemistry.

[8]  M. Carrington,et al.  A Dendritic Cell–Specific Intercellular Adhesion Molecule 3–Grabbing Nonintegrin (Dc-Sign)–Related Protein Is Highly Expressed on Human Liver Sinusoidal Endothelial Cells and Promotes HIV-1 Infection , 2001, The Journal of experimental medicine.

[9]  J. Trowsdale,et al.  Cutting Edge: DC-SIGN; a Related Gene, DC-SIGNR; and CD23 Form a Cluster on 19p131 2 , 2000, The Journal of Immunology.

[10]  Douglas S Kwon,et al.  DC-SIGN, a Dendritic Cell–Specific HIV-1-Binding Protein that Enhances trans-Infection of T Cells , 2000, Cell.

[11]  J. Goedert,et al.  Genetic effects on HIV disease progression , 1998, Nature Medicine.

[12]  M. Carrington,et al.  Persistently seronegative men from whom HIV-1 has been isolated are genetically and immunologically distinct. , 1996, Immunology Letters.

[13]  Steven M. Wolinsky,et al.  Human immunodeficiency virus type 1 infection in homosexual men who remain seronegative for prolonged periods. , 1989, The New England journal of medicine.

[14]  J. Phair,et al.  The Multicenter AIDS Cohort Study: rationale, organization, and selected characteristics of the participants. , 1987, American journal of epidemiology.

[15]  R. Kaslow,et al.  The impact of host genetics on HIV infection and disease progression in the era of highly active antiretroviral therapy. , 2003, AIDS.

[16]  J. Lang,et al.  Most highly exposed seronegative men lack HIV-1-specific, IFN-gamma-secreting T cells. , 2003, Journal of immunology.