title: Detrimental effects of mannose-binding lectin (MBL2) promoter genotype XA/XA on HIV-1 vertical transmission and AIDS progression.
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.affiliation: Laboratorio de Biología Celular y Retrovirus, Hospital de Pediatría Juan P. Garrahan, Buenos Aires, Argentina. ammangano@retrovirus.org
authors.forename: A
authors.initials: A
authors.lastname: Mangano
authors.forename: C
authors.initials: C
authors.lastname: Rocco
authors.forename: S M
authors.initials: SM
authors.lastname: Marino
authors.forename: D
authors.initials: D
authors.lastname: Mecikovsky
authors.forename: F
authors.initials: F
authors.lastname: Genre
authors.forename: P
authors.initials: P
authors.lastname: Aulicino
authors.forename: R
authors.initials: R
authors.lastname: Bologna
authors.forename: L
authors.initials: L
authors.lastname: Sen
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics*; D000483:Alleles; D002675:Child, Preschool; D015331:Cohort Studies; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015658:HIV Infections / Q000235:genetics / Q000635:transmission*; D015497:HIV-1; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D037601:Mannose-Binding Lectin / Q000097:blood / Q000235:genetics*; D016017:Odds Ratio
chemical_list: C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin