Gene frequency and partial protein characterization of an allelic variant of mannan binding protein associated with low serum concentrations

Abstract

SUMMARYLow 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 (eodon 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 (228%), and two homozygous for GAC (1-6"';.). The gene frequency ofthe GAC ailele was found to be 0-13, DNA sequencing ofthe cloned exon I from one GAC homozygous individual revealed no other substitution. The median MBP concentration in the group containing the GAC ailele was 6-4 times lower than in the GGC homozygous group (195 and 1234 p.%/1 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 /'g/0-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 alleie is able to produce a functional MBP protein which may be detected in serum at low concentrations.

Mannan-binding protein—levels in plasma and upper-airways secretions and frequency of genotypes in children with recurrence of otitis media

“…encoded in exon 1 ofihe MBP gene; 64 were homozygous Ibr Ihc GGC allele (71 9"/,,); 21 were heterozygous for the GAC allcle (23-5%); and four were homozygous for the GAC allele (4 5%), respectively (Table I), This gives a frequency ofthe GAC allele of 0-16. which is nol significantly differenl from that of healthy Danish controls (0-13) (/*-0-65) [20] (Fig. 3).…”

“…The variant allele causes an aminoacid substitution in exon I at codon 54 in the collagen-!ikc domain iti the MBP gene (GGC (glycine) to GAC (aspartic acid)). This mutatioti is remarkably frequent in both Caucasians and Eskimos, wilh an estimated allele frequeney of 013 in bolh populaiions [20,21], However, this mutation alone cannot account for all cases of MBP deficiency, because MBP deficiency was also seen in some individuals found with Ihe normal genotype (GGC). Another mutation associated with low MBP plasma concentrations at eodon57inexon 1 in the M BP gene ha.s been found in bolh Wesi and East Afriea.…”

“…In contrast, the MhoU restriction enzyme cleaves ihe African variant MBP GAA-type PCR product into two fragments and leaves the normal MBP GGA-type PCR prodtict undigested. Alternatively, the PCR product was hybridized with allele sequence-specific oligonucteotide probes recognizing GGC (5'-GG CGT GAT GGC ACC AAG G-3 ) and GAC (5'-GG CGT GAT GAC ACC AAG G-3 ) in the presence of letramelhylammonium chloride [20].…”

“…respectively. Subsequently restriction fragment length polymorphism analysis (RFLP) was performed [20], As a molecular weight marker pBR322 (Boehringer. Mannheim.…”

Polymorphisms in NRAMP1 and MBL2 genes and their relations with tuberculosis in Turkish children

“…In a Australian study involving 236 healthy blood donors, 30% were found to be heterozygous for structural gene mutations, and an additional 8% were homozygous or had double mutations of the structural genes (39). The codon 54 variant has an observed frequency of 42%-46% in South American Chiriguanos and Mapuches (40); in Danish, Midwestern American, and Greenland Eskimo population groups, the frequency is 11%-13% (41,42).…”