TY - JOUR

T1 - Different molecular events result in low protein levels of mannan-binding lectin in populations from southeast Africa and South America

AU - Madsen, H O

AU - Satz, M L

AU - Hogh, B

AU - Svejgaard, A

AU - Garred, P

PY - 1998/9/15

Y1 - 1998/9/15

N2 - 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.

AB - 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.

KW - Argentina/ethnology

KW - Base Sequence

KW - Carrier Proteins/blood

KW - Child

KW - Collectins

KW - Denmark/ethnology

KW - European Continental Ancestry Group/genetics

KW - Genetic Variation/immunology

KW - Genotype

KW - Haplotypes

KW - Humans

KW - Indians, South American/genetics

KW - Lectins/blood

KW - Mannans/blood

KW - Molecular Sequence Data

KW - Mozambique

KW - Prospective Studies

KW - Sequence Analysis, DNA

M3 - Journal article

C2 - 9743385

VL - 161

SP - 3169

EP - 3175

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 6

ER -