Immunoglobulin constant heavy G chain genes as risk factors in childhood allergies
Article first published online: 6 DEC 2006
Clinical & Experimental Allergy
Volume 36, Issue 12, pages 1616–1624, December 2006
How to Cite
Oxelius, V.-A., Bråbäck, L., Ahlstedt, S. and Björkstén, B. (2006), Immunoglobulin constant heavy G chain genes as risk factors in childhood allergies. Clinical & Experimental Allergy, 36: 1616–1624. doi: 10.1111/j.1365-2222.2006.02602.x
- Issue published online: 6 DEC 2006
- Article first published online: 6 DEC 2006
- Submitted 14 March 2006; revised 13 September 2006; accepted 19 September 2006
- allergic rhinitis;
- allergy heredity;
- alternative IgG subclass allotypes;
- IGHG alleles;
- IGHG diplotypes;
- IGHG genotypes;
- IGHG haplotypes (=B-cells);
Background Several candidate genes have been found to be associated with the inflammatory response of IgE-mediated allergy, so also the immunoglobulin constant heavy G chain (IGHG) genes. The IGHG genes are situated close to the IGHE gene on chromosome 14q32, 5′μ, δ, γ3, γ1, α1, γ2, γ4, ɛ, α2, 3′. They are inherited in a Mendelian fashion and expressed randomly in allelic exclusion. The alternative and functionally different γ3, γ1 and γ2 gene variants are found in four IGHG haplotypes, coding four B cell variants.
Objective The aim of this study was to assess the frequency of different IGHG genes in relation to phenotypes associated with allergy, in a case–control study.
Methods We identified the constant heavy-chain genes of IgG in 198 allergic and non-allergic children participating in the Phase II of the International Study of Asthma and Allergy in Children. The IGHG genes were assessed by the alternative serum IgG subclass allotypes expressing the alternative alleles of γ3, γ1 and γ2 genes, using ELISA and double immunodiffusion.
Results The IGHG*bfn haplotype (=B1 cells) and IGHG2*n allele dominated (51% vs. 24%, P=0.002) and the IGHG*bf-n haplotype (=B2 cells) was infrequent (16% vs. 52%, P<0.001) in allergic children with a family history of allergy, clinical manifest allergy and positive skin prick test (SPT). The frequency of IGHG genes was similar in children with maternal and paternal heredity and in children with wheezing, eczema or rhinitis, as well as in children with different positive SPT. The IGHG*bfn haplotype with the IGHG2*n allele was strongly associated with heredity for allergy. The IGHG*bf-n haplotype was inversely related to allergy.
Conclusions IgG allotypes, immunochemical and functional variants of IgG molecules from IGHG genes are associated with atopy. The IGHG*bfn haplotype (=B1 cells) with the IGHG2*n allele dominates, associated with an increased risk for atopy. In contrast, the IGHG*bf-n haplotype (=B2 cells) with the IGHG2*-n allele is associated with low risk.