Polymorphisms in the MBL2 promoter correlated with risk of HIV-1 vertical transmission and AIDS progression.

Genetic Service, IRCCS Burlo Garofolo and Chair of Genetics, University of Trieste, Via dell'Istria 65/1, 34137 Trieste, Italy.
Genes and Immunity (Impact Factor: 3.79). 07/2000; 1(5):346-8. DOI: 10.1038/sj.gene.6363685
Source: PubMed

ABSTRACT We investigated the polymorphisms of the promoter region of the MBL2 gene, which codifies for the Mannose-binding protein (MBP). The study population included 90 children with vertically acquired HIV-infection, further divided on the basis of the disease rate, 27 HIV exposed-uninfected children, and 74 healthy control subjects matched for ethnic origin to evaluate the MBP involvement in the risk of HIV-1 infection and to assess the role of the MBP promoter in AIDS progression. A region of 380 bp in the promoter of the MBL2 gene was analysed by PCR and direct sequencing of both DNA strands. We found that the polymorphism at position -550 influences the risk of HIV-infection and AIDS progression. Also a 6 bp deletion at position -328 was correlated with HIV-1 infection. This study indicates that the promoter of the MBL2 gene influences vertical transmission of HIV and the course of perinatal infection.

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    ABSTRACT: Abstract Mannose binding lectin (MBL) is a pathogen pattern recognition protein involved in antimicrobial activities. Variation in MBL2 gene has been extensively implicated in differential outcomes of infectious diseases in studies conducted outside Africa, but virtually very little is known on the role of this candidate gene in the African continent. We investigated human genetic variations in MBL2 in a Zimbabwean pediatric population and their putative associations with HIV infection in perinatally exposed children. One hundred and four children aged 7 to 9 years comprising 68 perinatally exposed to HIV (32 who were born infected and 36 who were uninfected) and 36 unexposed controls were recruited. DNA samples were genotyped for MBL2 polymorphisms using PCR-RFLP and sequencing. HIV infected children had markedly variable and significantly lower mean height (p=0.03) and weight (p=0.005) when compared to the uninfected children. Using all samples, frequencies for MBL2 genetic variants for the Zimbabwean population were calculated. Twelve single nucleotide polymorphisms were observed and minor alleles occurred with the following frequencies: -550C>G (G: 0.02), -435G>A (A: 0.08), -428A>C (C: 0.39), -394A>G (A: 0.39), -328AGAGAA ins/del (AGAGAA ins: 0.44), -245G>A (A: 0.05), -221C>G (C: 0.12), -111A>T (T: 0.10), -70C>T (C: 0.46), +4C>T (C: 0.45), novel -595G>A (A: 0.02), and 170G>A (0.24). We found that the MBL2 +4T variant displayed a trend for association with reduced risk of HIV transmission from mother-to-child but the remaining vast majority of the genetic markers did not show a significant association. We conclude (1) the MBL2 gene is highly polymorphic in the Zimbabwean population, and (2) MBL2 genetic variation does not appear to play a major role in influencing the risk of mother-to-child HIV transmission in our study sample. These observations contest the hitherto significant role of this candidate gene for HIV transmission from mother-to-child in non-African populations and thus, further speak to the limits of extrapolating genomic association studies directly to the African populations from studies conducted elsewhere. It is hoped that more OMICS research in a diverse set of African countries can shed further light on the putative role (or the lack thereof ) of this candidate gene in HIV transmission in the continent, a major global health burden in Africa.
    Omics: a journal of integrative biology 03/2014; · 2.29 Impact Factor
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    ABSTRACT: Background: Human Mannose-binding lectin (MBL) encoded by the MBL2 gene is a pattern-recognition protein and have been associated with many infectious diseases including malaria. We aim to investigate the contribution of functional MBL2 gene variations with P. falciparum malaria in well-defined cases and in matched controls.Methods: We re-sequenced the 8.7kb of the entire MBL2 gene in 434 clinically classified malaria individuals from malaria endemic regions of India. The study cohort includes 176 patients with severe malaria, 101 with mild malaria and 157 ethnically matched asymptomatic individuals. Additionally, 830 individuals from 32 socially, linguistically and geographically diverse endogamous populations of India were investigated for the distribution of functional MBL2 variants.Results: The MBL2-221C (X) allelic variant is associated with increased risk of malaria (mild malaria OR: 1.9, P(Corr)=0.0036; severe malaria OR: 1.6, P(Corr)=0.02). The exon1 variants MBL2*B (severe malaria OR: 2.1, P(Corr)=0.036; mild vs. severe malaria OR: 2.5, P(Corr)=0.039) and MBL2*C (mild vs. severe malaria OR: 5.4, P(Corr)=0.045) increase the odds of malaria. The exon1 MBL2*D/*B/*C variant increases the risk towards severe malaria (OR:3.4, P(Corr)=0.000045). The frequencies of low MBL haplotypes were significantly higher in severe malaria (14.2%) compared to mild malaria (7.9%) and asymptomatic (3.8%). The MBL2*LYPA haplotypes confers protection whereas MBL2*LXPA increases the malaria risk.Conclusions: Our first findings in Indian populations demonstrate that MBL2 functional variants are strongly associated with malaria and infection severity.
    Infection and immunity 10/2013; · 4.16 Impact Factor
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    ABSTRACT: The pattern recognition molecules of the lectin complement pathway are important components of the innate immune system with known functions in host-virus interactions. This paper summarizes current knowledge of how these intriguing molecules, including mannose-binding lectin (MBL), ficolin-1, -2 and -3, and collectin-11 (CL-11) may influence HIV-pathogenesis. It has been demonstrated that MBL is capable of binding and neutralizing HIV and may affect host susceptibility to HIV infection and disease progression. In addition, MBL may cause variations in the host immune response against HIV. Ficolin-1, -2 and -3 and CL-11 could have similar functions in HIV infection as the ficolins have been shown to play a role in other viral infections, and CL-11 resembles MBL and the ficolins in structure and binding capacity.
    Clinical Immunology 06/2014; · 3.99 Impact Factor

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