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.
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: Joanne Nititham; Rashmi Gupta; Xue Zeng; Wendy Hartogensis; Douglas F Nixon; Steven G Deeks; Frederick M Hecht; Wilson Liao Journal: Hum Immunol Date: 2016-10-31 Impact factor: 2.850
Authors: Rutendo B L Zinyama-Gutsire; Charles Chasela; Per Kallestrup; Simbarashe Rusakaniko; Michael Christiansen; Bernard Ngara; Exnevia Gomo; Henrik Ullum; Christian Erikstrup; Hans O Madsen; Babill Stray-Pedersen; Peter Garred; Takafira Mduluza Journal: OMICS Date: 2015-09
Authors: Geneviève Boily-Larouche; Miroslav P Milev; Lynn S Zijenah; Annie-Claude Labbé; Djimon M Zannou; Jean H Humphrey; Brian J Ward; Johanne Poudrier; Andrew J Mouland; Eric A Cohen; Michel Roger Journal: PLoS One Date: 2012-07-10 Impact factor: 3.240
Authors: Rutendo B L Zinyama-Gutsire; Charles Chasela; Hans O Madsen; Simbarashe Rusakaniko; Per Kallestrup; Michael Christiansen; Exnevia Gomo; Henrik Ullum; Christian Erikstrup; Shungu Munyati; Edith N Kurewa; Babill Stray-Pedersen; Peter Garred; Takafira Mduluza Journal: PLoS One Date: 2015-04-01 Impact factor: 3.240
Authors: Geneviève Boily-Larouche; Anne-Laure Iscache; Lynn S Zijenah; Jean H Humphrey; Andrew J Mouland; Brian J Ward; Michel Roger Journal: PLoS One Date: 2009-10-07 Impact factor: 3.240