Independent effects of genetic variations in mannose-binding lectin influence the course of HIV disease: The advantage of heterozygosity for coding mutations

Gabriel Catano, Brian K. Agan, Hemant Kulkarni, Vanessa Telles, Vincent C. Marconi, Matthew J. Dolan, Sunil K Ahuja

Research output: Contribution to journalArticle

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Abstract

Background. The in vivo impact of mannose-binding lectin (MBL), a molecule involved in innate immunity, on the pathogenesis of human immunodeficiency virus (HIV)-1 infection and AIDS is unknown. Methods. A total of 1102 HIV-positive and 2213 HIV-negative adult subjects were screened for polymorphisms in the coding and promoter regions of MBL2, the gene that encodes MBL. Results. Variations in MBL2 did not influence the risk of acquiring HIV-1. Heterozygosity for coding mutations (O allele) and homozygosity for the -221 promoter polymorphism (X allele) in MBL2 were associated with a delay in and an accelerated rate of disease progression, respectively. MBL2 variations influenced the rate of progression to AIDS-defining illnesses. In a multivariate model, the effects of MBL2 variations were independent of several parameters known to influence disease progression, including steady-state viral load, baseline CD4+ T cell counts, and delayed-type hypersensitivity skin test responses, an in vivo marker of cell-mediated immunity. The effects of MBL2 variations were most evident in those who possessed protective genotypes of CCR5 and a high copy number of CCL3L1, the most potent HIV-suppressive CCR5 ligand. Conclusions. MBL2 genotypes are independent determinants of HIV disease progression and heterozygosity for MBL2 coding mutations confer disease-retarding effects. MBL-dependent immune responses may play a role in the pathogenesis of HIV infection.

Original languageEnglish (US)
Pages (from-to)72-80
Number of pages9
JournalJournal of Infectious Diseases
Volume198
Issue number1
DOIs
StatePublished - Jul 1 2008

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Mannose-Binding Lectin
Virus Diseases
HIV
Mutation
Disease Progression
HIV-1
Acquired Immunodeficiency Syndrome
Alleles
Genotype
Delayed Hypersensitivity
CD4 Lymphocyte Count
Skin Tests
Viral Load
Innate Immunity
Genetic Promoter Regions
Cellular Immunity
Ligands
T-Lymphocytes
Genes

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

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Independent effects of genetic variations in mannose-binding lectin influence the course of HIV disease : The advantage of heterozygosity for coding mutations. / Catano, Gabriel; Agan, Brian K.; Kulkarni, Hemant; Telles, Vanessa; Marconi, Vincent C.; Dolan, Matthew J.; Ahuja, Sunil K.

In: Journal of Infectious Diseases, Vol. 198, No. 1, 01.07.2008, p. 72-80.

Research output: Contribution to journalArticle

Catano, Gabriel ; Agan, Brian K. ; Kulkarni, Hemant ; Telles, Vanessa ; Marconi, Vincent C. ; Dolan, Matthew J. ; Ahuja, Sunil K. / Independent effects of genetic variations in mannose-binding lectin influence the course of HIV disease : The advantage of heterozygosity for coding mutations. In: Journal of Infectious Diseases. 2008 ; Vol. 198, No. 1. pp. 72-80.
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abstract = "Background. The in vivo impact of mannose-binding lectin (MBL), a molecule involved in innate immunity, on the pathogenesis of human immunodeficiency virus (HIV)-1 infection and AIDS is unknown. Methods. A total of 1102 HIV-positive and 2213 HIV-negative adult subjects were screened for polymorphisms in the coding and promoter regions of MBL2, the gene that encodes MBL. Results. Variations in MBL2 did not influence the risk of acquiring HIV-1. Heterozygosity for coding mutations (O allele) and homozygosity for the -221 promoter polymorphism (X allele) in MBL2 were associated with a delay in and an accelerated rate of disease progression, respectively. MBL2 variations influenced the rate of progression to AIDS-defining illnesses. In a multivariate model, the effects of MBL2 variations were independent of several parameters known to influence disease progression, including steady-state viral load, baseline CD4+ T cell counts, and delayed-type hypersensitivity skin test responses, an in vivo marker of cell-mediated immunity. The effects of MBL2 variations were most evident in those who possessed protective genotypes of CCR5 and a high copy number of CCL3L1, the most potent HIV-suppressive CCR5 ligand. Conclusions. MBL2 genotypes are independent determinants of HIV disease progression and heterozygosity for MBL2 coding mutations confer disease-retarding effects. MBL-dependent immune responses may play a role in the pathogenesis of HIV infection.",
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