AEGiS-14IAC: Mannose-binding lectin B Allele is associated with slower progression to AIDS in perinatally HIV-1 infected children.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Mannose-binding lectin B Allele is associated with slower progression to AIDS in perinatally HIV-1 infected children.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. A10064)

Mangano A, Mecikovsky D, Kopka J, Batalla M, Ruvinsky S, Bologna R, Sen L
Hospital Nacional de Pediatria, Buenos Aires, Argentina

BACKGROUND: Host genetic background can influence susceptibility to HIV-1 infection and disease progression. Mannose-binding lectin (MBL) is recognized as an important factor of innate immunity. Three different mutations in the exon 1 of MBL gene lower serum concentration of MBL, which impair opsonisation and phagocitosis. The wild type allele is called A and the variants are B (Gly54Asp), C (Gly57Glut) and D (Arg52Cys). OBJECTIVES: a) To establish the frequency of MBL variants in Argentine population; b) To analyze whether the MBL alleles are associated with HIV-1 susceptibility and disease progression in a pediatric cohort perinatally exposed to HIV-1. Material and

METHODS: We investigated the presence of MBL genetic variants in 95 blood donors (control population) and 285 HIV-1 exposed children (98 infected and 187 uninfected). MBL genotyping was assessed by PCR-RFLP assays. Survival analyses were performed to determine the association between MBL genotypes and time to AIDS.

RESULTS: Of the MBL variants only the B allele was identified in Argentine population with a frequency of 20.5% (30% A/B heterozygotes; 5% B/B homozygotes). The distribution of the B allele did not differ between infected (20.4%) and uninfected children(20.1%) and was similar to control population. Of the 61 infected children with a clinical follow-up at our Hospital, 44 developed AIDS. Kaplan-Meier analysis of time to AIDS showed that children carriers of MBL B allele (n=26) progressed to AIDS significantly slower than MBL wild type (n=35) (p=0.03, log rank test), with median AIDS-free survival time of 64 months and 18 months, respectively.

CONCLUSIONS: The MBL B allele was the only genetic variant present in our population and is more frequent compared to other Caucasian populations (20% vs. 5-10%). The B allele does not seem to affect HIV-1 mother-to child transmission whereas significantly protects against progression to AIDS.

Keywords: AEGIS, HIV-1, Acquired Immunodeficiency Syndrome, Alleles, HIV Infections, Plant Lectins, Disease Progression, Mannose-Binding Lectin, Genotype, Variation (Genetics), Exons, Heterozygote, Polymerase Chain Reaction, Polymorphism, Restriction Fragment Length, DNA Primers, Mutation, lectin B, Phytolacca americana, Child, Human, genetics

020707
A10064