A variable number of tandem repeats polymorphism influences the transcriptional activity of the neonatal Fc receptor α‐chain promoter

Summary The neonatal Fc receptor, FcRn, plays a central role in immunoglobulin G (IgG) transport across placental barriers. Genetic variations of FcRn‐dependent transport across the placenta may influence antibody‐mediated pathologies of the fetus and the newborn. Sequencing analysis of 20 unrelated...

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Bibliographic Details
Published in:Immunology 2006-09, Vol.119 (1), p.83-89
Main Authors: Sachs, Ulrich J. H., Socher, Ines, Braeunlich, Christian G., Kroll, Hartmut, Bein, Gregor, Santoso, Sentot
Format: Article
Language:English
Subjects:
Alleles
Cells, Cultured
Gene Expression
Genetic Variation
Heterozygote
Histocompatibility Antigens Class I - genetics
Homozygote
Humans
IgG
Immunoglobulin G - metabolism
Infant, Newborn
Monocytes - metabolism
neonatal Fc receptor
Original
promoter polymorphism
Promoter Regions, Genetic - genetics
Protein Binding
Receptors, Fc - genetics
Statistics, Nonparametric
Tandem Repeat Sequences
Transcription, Genetic
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Summary:Summary The neonatal Fc receptor, FcRn, plays a central role in immunoglobulin G (IgG) transport across placental barriers. Genetic variations of FcRn‐dependent transport across the placenta may influence antibody‐mediated pathologies of the fetus and the newborn. Sequencing analysis of 20 unrelated individuals demonstrated no missense mutation within the five exons of the FcRn gene. However, a variable number of tandem repeats (VNTR) region within the FcRn promoter was observed, consisting of five different alleles (VNTR1–VNTR5). Alleles with two (VNTR2) and three (VNTR3) repeats were found to be most common in Caucasians (7·5 and 92·0%, respectively). Real‐time polymerase chain reaction revealed that monocytes from VNTR3 homozygous individuals express 1·66‐fold more FcRn transcript than do monocytes from VNTR2/VNTR3 heterozygous individuals (P = 0·002). In reporter plasmid assays, the VNTR3 allele supported the transcription of a reporter gene twice as effectively as did the VNTR2 allele (P = 0·003). Finally, under acidic conditions, monocytes from VNTR3 homozygous individuals showed an increased binding to polyvalent human IgG when compared with monocytes from VNTR2/VNTR3 heterozygous individuals (P = 0·021). These data indicate that a VNTR promoter polymorphism influences the expression of the FcRn receptor, leading to different IgG‐binding capacities.
ISSN:0019-2805
1365-2567
DOI:10.1111/j.1365-2567.2006.02408.x