Immunoglobulin constant heavy G chain genes as risk factors in childhood allergies

• Published in: Clinical and experimental allergy Vol. 36; no. 12; pp. 1616 - 1624
• Main Authors: Oxelius, V.-A., Bråbäck, L., Ahlstedt, S., Björkstén, B.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.2006; Blackwell
• Subjects: Alleles; Allergic diseases; allergic rhinitis; allergy heredity; alternative IgG subclass allotypes; Biological and medical sciences; Case-Control Studies; Child; Clinical Medicine; eczema; Enzyme-Linked Immunosorbent Assay; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Frequency; Genetic Markers; Genetic Predisposition to Disease; Genotype; Haplotypes; Health Surveys; Humans; Hypersensitivity - blood; Hypersensitivity - genetics; Hypersensitivity - immunology; IGHG alleles; IGHG diplotypes; IGHG genotypes; IGHG haplotypes (=B-cells); Immunoglobulin Constant Regions - genetics; Immunoglobulin G - blood; Immunoglobulin G - genetics; Immunoglobulin Gm Allotypes - genetics; Immunopathology; Klinisk medicin; Logistic Models; Lungmedicin och allergi; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; Odds Ratio; Respiratory Medicine and Allergy; Skin allergic diseases. Stinging insect allergies; SPT; Sweden; wheezing; Sweden; Allergy; Nose disease; Skin disease; Rhinitis; IgG; allergy heredity; Wheezing; Epidemiology; IGHG genotypes; Immunology; Gene; SPT; Eczema; ENT disease; Genetics; Child; Haplotype; Human; Immunopathology; Heavy peptide chain; Allotype; Genotype; B-Lymphocyte; Allele; IGHG alleles; alternative IgG subclass allotypes; Risk factor; IGHG diplotypes; Inheritance(genetics); allergic rhinitis; IGHG haplotypes (= B-cells)
• ISSN: 0954-7894; 1365-2222; 1365-2222
• DOI: 10.1111/j.1365-2222.2006.02602.x

Summary 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.