title: Diallelic polymorphism may explain variations of the blood concentration of mannan-binding protein in Eskimos, but not in black Africans.
abstract: Mannan-binding protein (MBP) is a lectin which, upon binding to certain carbohydrates, activates the classical pathway of complement without the involvement of antibody or C1q. Deficiency of the MBP is associated with an opsonic defect and recurrent infections during early life. An amino acid substitution in the exon 1 at codon 54 in the MBP gene (GGC [glycine] to GAC [aspartic acid]) has been shown to be closely associated with low MBP concentration in Caucasoids. The gene frequency of the mutant allele in this population has been estimated at 0.13. In the study described here, we investigated the association between the mutant allele and MBP protein concentration in Eskimos from East-Greenland and black Africans from the Baringo District in Kenya. The frequency of the GAC allele was identical in Eskimos and Caucasoids (0.13). No overlap with regard to MBP concentration between the genotypes was found in the Eskimos. In contrast, the Africans revealed a low frequency of the GAC allele (0.009). However, the median MBP protein concentration was approximately 5 times lower among the Africans than the Eskimos. In 12.6% of the Africans and in 2.5% of the Eskimos, MBP was undetectable. Thus, MBP deficiency is the most frequent immunodeficiency so far described. The high prevalence of MBP deficiency among healthy individuals indicates that MBP deficiency also confers some selective advantages. We advance the hypothesis that MBP deficiency is maintained in populations because MBP deficiency decreases the infectivity of some intracellular micro-organisms which are dependent on opsonization.
authors: Department of Clinical Immunology, State University Hospital, Copenhagen, Denmark.
authors: P
authors: P
authors: Garred
authors: H O
authors: HO
authors: Madsen
authors: J A
authors: JA
authors: Kurtzhals
authors: L U
authors: LU
authors: Lamm
authors: S
authors: S
authors: Thiel
authors: A S
authors: AS
authors: Hey
authors: A
authors: A
authors: Svejgaard
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D044466:Asian People; D001483:Base Sequence; D044383:Black People; D002352:Carrier Proteins / Q000097:blood* / Q000235:genetics*; D037222:Collectins; D004247:DNA / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006116:Greenland; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000097:blood / Q000235:genetics; D004930:Inuit; D007630:Kenya; D008297:Male; D008351:Mannans / Q000378:metabolism*; D008875:Middle Aged; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic
chemical_list: D002352:Carrier Proteins; D037222:Collectins; D008351:Mannans; D004247:DNA