title: Gene frequency and partial protein characterization of an allelic variant of mannan binding protein associated with low serum concentrations.
abstract: Low plasma concentration of mannan binding protein (MBP) has been shown to be the basis for a common opsonic deficiency and suggested to be caused by a single nucleotide substitution at base 230 of exon 1 in the MBP gene. This substitution causes a replacement of glycine (codon GGC) with aspartic acid (codon GAC). Of 123 healthy Danish individuals investigated by polymerase chain reaction performed on exon 1, followed by restriction fragment length polymorphism or allospecific probing, 93 were homozygous (75.6%) for GGC, 28 heterozygous (22.8%), and two homozygous for GAC (1.6%). The gene frequency of the GAC allele was found to be 0.13. DNA sequencing of the cloned exon 1 from one GAC homozygous individual revealed no other substitution. The median MBP concentration in the group containing the GAC allele was 6.4 times lower than in the GGC homozygous group (195 and 1234 micrograms/l respectively). However, the range in plasma concentrations of MBP was wide and overlapping between the groups. MBP protein was detected in both the GAC homozygotes (9 and 387 micrograms/l). Furthermore, no difference in relative mass and biological activity (mannan binding) was found when sera containing the two forms of MBP were investigated. Accordingly, it can be concluded that the GAC allele is able to produce a functional MBP protein which may be detected in serum at low concentrations.
authors.affiliation: Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: P
authors.initials: P
authors.lastname: Garred
authors.forename: S
authors.initials: S
authors.lastname: Thiel
authors.forename: H O
authors.initials: HO
authors.lastname: Madsen
authors.forename: L P
authors.initials: LP
authors.lastname: Ryder
authors.forename: J C
authors.initials: JC
authors.lastname: Jensenius
authors.forename: A
authors.initials: A
authors.lastname: Svejgaard
mesh_terms: D000328:Adult; D000483:Alleles; D001483:Base Sequence; D002352:Carrier Proteins / Q000097:blood* / Q000235:genetics*; D037222:Collectins; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction
chemical_list: D002352:Carrier Proteins; D037222:Collectins