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Detrimental effects of mannose-binding lectin (MBL2) promoter genotype XA/XA on HIV-1 vertical transmission and AIDS progression.
J Infect Dis. 2008 Sep 01; 198(5):694-700.JI

Abstract

BACKGROUND

The literature on the involvement of mannose-binding lectin (MBL) in human immunodeficiency virus (HIV) transmission and acquired immunodeficiency syndrome (AIDS) is conflicting. Polymorphisms in the MBL2 gene reduce the level of protein and alter its structure. Thus, we investigated whether MBL2 alleles and plasma concentrations of MBL are associated with perinatal HIV transmission and disease progression.

METHODS

Frequencies of MBL2 allelic variants (B, C, D, and X) were estimated among 345 HIV-exposed children and 147 blood donors. AIDS-free time was evaluated for different MBL2 genotypes and MBL plasma levels. The median duration of follow-up was 96.5 months.

RESULTS

In the Argentinean population, gene frequencies of MBL2 variants were 18%, 15%, and 3% for the X, B, and D alleles, respectively, with no identified C allele. The haplotype XA/XA was associated with an 8-fold risk of acquiring HIV-1 (P= .054; odds ratio [OR], 8.11 [95% confidence interval {CI}, 0.96-67.86]) and almost a 3-fold risk of progression to pediatric AIDS (P= .026; OR, 2.81 [95% CI, 1.14-7.47]). We also found an independent positive correlation between the rate of AIDS progression and MBL plasma concentration (P= .008; OR, 1.28 [95% CI, 1.07-1.55]).

CONCLUSIONS

Our results demonstrate that homozygosity for the MBL2 promoter genotype XA/XA is an important genetic determinant of HIV-1 acquisition through vertical transmission and the pathogenesis of pediatric HIV/AIDS, via a mechanism that remains to be established.

Authors+Show Affiliations

Laboratorio de Biología Celular y Retrovirus, Hospital de Pediatría Juan P. Garrahan, Buenos Aires, Argentina. ammangano@retrovirus.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18637753

Citation

Mangano, A, et al. "Detrimental Effects of Mannose-binding Lectin (MBL2) Promoter Genotype XA/XA On HIV-1 Vertical Transmission and AIDS Progression." The Journal of Infectious Diseases, vol. 198, no. 5, 2008, pp. 694-700.
Mangano A, Rocco C, Marino SM, et al. Detrimental effects of mannose-binding lectin (MBL2) promoter genotype XA/XA on HIV-1 vertical transmission and AIDS progression. J Infect Dis. 2008;198(5):694-700.
Mangano, A., Rocco, C., Marino, S. M., Mecikovsky, D., Genre, F., Aulicino, P., Bologna, R., & Sen, L. (2008). Detrimental effects of mannose-binding lectin (MBL2) promoter genotype XA/XA on HIV-1 vertical transmission and AIDS progression. The Journal of Infectious Diseases, 198(5), 694-700. https://doi.org/10.1086/590498
Mangano A, et al. Detrimental Effects of Mannose-binding Lectin (MBL2) Promoter Genotype XA/XA On HIV-1 Vertical Transmission and AIDS Progression. J Infect Dis. 2008 Sep 1;198(5):694-700. PubMed PMID: 18637753.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Detrimental effects of mannose-binding lectin (MBL2) promoter genotype XA/XA on HIV-1 vertical transmission and AIDS progression. AU - Mangano,A, AU - Rocco,C, AU - Marino,S M, AU - Mecikovsky,D, AU - Genre,F, AU - Aulicino,P, AU - Bologna,R, AU - Sen,L, PY - 2008/7/22/pubmed PY - 2008/10/1/medline PY - 2008/7/22/entrez SP - 694 EP - 700 JF - The Journal of infectious diseases JO - J. Infect. Dis. VL - 198 IS - 5 N2 - BACKGROUND: The literature on the involvement of mannose-binding lectin (MBL) in human immunodeficiency virus (HIV) transmission and acquired immunodeficiency syndrome (AIDS) is conflicting. Polymorphisms in the MBL2 gene reduce the level of protein and alter its structure. Thus, we investigated whether MBL2 alleles and plasma concentrations of MBL are associated with perinatal HIV transmission and disease progression. METHODS: Frequencies of MBL2 allelic variants (B, C, D, and X) were estimated among 345 HIV-exposed children and 147 blood donors. AIDS-free time was evaluated for different MBL2 genotypes and MBL plasma levels. The median duration of follow-up was 96.5 months. RESULTS: In the Argentinean population, gene frequencies of MBL2 variants were 18%, 15%, and 3% for the X, B, and D alleles, respectively, with no identified C allele. The haplotype XA/XA was associated with an 8-fold risk of acquiring HIV-1 (P= .054; odds ratio [OR], 8.11 [95% confidence interval {CI}, 0.96-67.86]) and almost a 3-fold risk of progression to pediatric AIDS (P= .026; OR, 2.81 [95% CI, 1.14-7.47]). We also found an independent positive correlation between the rate of AIDS progression and MBL plasma concentration (P= .008; OR, 1.28 [95% CI, 1.07-1.55]). CONCLUSIONS: Our results demonstrate that homozygosity for the MBL2 promoter genotype XA/XA is an important genetic determinant of HIV-1 acquisition through vertical transmission and the pathogenesis of pediatric HIV/AIDS, via a mechanism that remains to be established. SN - 0022-1899 UR - https://www.unboundmedicine.com/medline/citation/18637753/Detrimental_effects_of_mannose_binding_lectin__MBL2__promoter_genotype_XA/XA_on_HIV_1_vertical_transmission_and_AIDS_progression_ L2 - https://academic.oup.com/jid/article-lookup/doi/10.1086/590498 DB - PRIME DP - Unbound Medicine ER -