Different Molecular Events Result in Low Protein Levels of Mannan-Binding Lectin in Populations from Southeast Africa and South America

Previous studies have shown that three point mutations in exon 1 and a particular promoter haplotype of the mannan-binding lectin (MBL) gene lead to a dramatic decrease in the serum concentration of MBL. In this study, MBL genotypes and serum concentrations were determined in unrelated individuals i...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of immunology (1950) 1998-09, Vol.161 (6), p.3169-3175
Main Authors: Madsen, Hans O, Satz, M. Leonardo, Hogh, Birthe, Svejgaard, Arne, Garred, Peter
Format: Article
Language:English
Subjects:
Argentina - ethnology
Base Sequence
Carrier Proteins - blood
Carrier Proteins - genetics
Child
Collectins
Denmark - ethnology
European Continental Ancestry Group - genetics
Genetic Variation - immunology
Genotype
Haplotypes
Humans
Indians, South American - genetics
Lectins - blood
Lectins - genetics
Mannans - blood
Mannans - genetics
Molecular Sequence Data
Mozambique
Prospective Studies
Sequence Analysis, DNA
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Previous studies have shown that three point mutations in exon 1 and a particular promoter haplotype of the mannan-binding lectin (MBL) gene lead to a dramatic decrease in the serum concentration of MBL. In this study, MBL genotypes and serum concentrations were determined in unrelated individuals in a population from Mozambique (n = 154) and in two native Indian tribes from Argentina (i.e., the Chiriguanos (n = 43) and the Mapuches (n = 25)). In both populations, the MBL concentrations were low compared with those found in Eskimo, Asian, and European populations. In Africans, the low serum concentrations were due to a high allele frequency (0.24) of the codon 57 (C) variant, which resulted in a high frequency of individuals with MBL deficiency (0.06), and were also due to the effect of a relatively high frequency (0.13) of low-producing promoter haplotypes. The low concentrations in the South American populations were primarily due to an extremely high allele frequency of the codon 54 (B) variant in both the Chiriguanos (0.42) and the Mapuches (0.46), resulting in high frequencies of individuals with MBL deficiency (0.14 and 0.16, respectively). In the search for additional genetic variants, we found five new promoter mutations that might help to elucidate the evolution of the MBL gene. Taken together, the results of this study show that different molecular mechanisms are the basis for low MBL levels on the two continents.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.161.6.3169