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Two loci on chromosome 5 are associated with serum IgE levels in Labrador retrievers.

Owczarek-Lipska M, Lauber B, Molitor V, Meury S, Kierczak M, Tengvall K, Webster MT, Jagannathan V, Schlotter Y, Willemse T, Hendricks A, Bergvall K, Hedhammar A, Andersson G, Lindblad-Toh K, Favrot C, Roosje P, Marti E, Leeb T - PLoS ONE (2012)

Bottom Line: We identified a genome-wide significant association on CFA 5 with the antigen-specific IgE responsiveness to Acarus siro.We detected a second genome-wide significant association with respect to the antigen-specific IgE responsiveness to Tyrophagus putrescentiae at a different locus on chromosome 5.No obvious candidate gene for the regulation of IgE levels is located under the two association signals.

View Article: PubMed Central - PubMed

Affiliation: Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.

ABSTRACT
Crosslinking of immunoglobulin E antibodies (IgE) bound at the surface of mast cells and subsequent mediator release is considered the most important trigger for allergic reactions. Therefore, the genetic control of IgE levels is studied in the context of allergic diseases, such as asthma, atopic rhinitis, or atopic dermatitis (AD). We performed genome-wide association studies in 161 Labrador Retrievers with regard to total and allergen-specific immunoglobulin E (IgE) levels. We identified a genome-wide significant association on CFA 5 with the antigen-specific IgE responsiveness to Acarus siro. We detected a second genome-wide significant association with respect to the antigen-specific IgE responsiveness to Tyrophagus putrescentiae at a different locus on chromosome 5. A. siro and T. putrescentiae both belong to the family Acaridae and represent so-called storage or forage mites. These forage mites are discussed as major allergen sources in canine AD. No obvious candidate gene for the regulation of IgE levels is located under the two association signals. Therefore our studies offer a chance of identifying a novel mechanism controlling the host's IgE response.

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ELISA measurements of 15 immunological phenotypes depending on the genotype at SNP BICF2S2297212.The G-allele at this SNP was associated with the allergen-specific IgE response to A. siro. Note that dogs with the homozygous G/G genotype show a consistent trend for higher IgE levels across all measured antigens. Boxes represent the 25th and 75th percentile of the phenotypic distribution with the median indicated by a solid horizontal line. The whiskers indicate the minimum and maximum of the distributions. Outliers that are more than 1.5 times the interquartile range away from the median are shown as open circles. Abbreviations for allergens: Df, Dermatophagoides farinae; Dp, Dermatophagoides pteronyssinus; Tp, Tyrophagus putrescentiae; Ld, Lepidoglyphus destructor; As, Acarus siro; Aa, Alternaria alternate; Ch, Cladosporium herbarum; Af, Aspergillus fumigates; Ps, Penicillinum sp.; Cat, cat epithelium; Flea, flea saliva; Bg, Blattela germanica.
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pone-0039176-g003: ELISA measurements of 15 immunological phenotypes depending on the genotype at SNP BICF2S2297212.The G-allele at this SNP was associated with the allergen-specific IgE response to A. siro. Note that dogs with the homozygous G/G genotype show a consistent trend for higher IgE levels across all measured antigens. Boxes represent the 25th and 75th percentile of the phenotypic distribution with the median indicated by a solid horizontal line. The whiskers indicate the minimum and maximum of the distributions. Outliers that are more than 1.5 times the interquartile range away from the median are shown as open circles. Abbreviations for allergens: Df, Dermatophagoides farinae; Dp, Dermatophagoides pteronyssinus; Tp, Tyrophagus putrescentiae; Ld, Lepidoglyphus destructor; As, Acarus siro; Aa, Alternaria alternate; Ch, Cladosporium herbarum; Af, Aspergillus fumigates; Ps, Penicillinum sp.; Cat, cat epithelium; Flea, flea saliva; Bg, Blattela germanica.

Mentions: We further analyzed whether there are any correlations between the A. siro-specific IgE responsiveness and the other studied traits. The best-associated SNP for this trait was BICF2S2297212 (Table 1). The A-allele at this SNP had a frequency of 7.8% and occurred almost exclusively in A. siro-specific IgE non-responsive dogs. When we grouped the dogs according to their genotypes at the associated SNP, we observed a consistent trend for dogs with the A-allele to have lower total and lower allergen-specific IgE levels with respect to all tested allergens compared to the dogs that were homozygous G/G. The genotype at this SNP had no visible correlation with the Dermatophagoides farinae-specific IgG1 or IgG4 levels (Figure 3).


Two loci on chromosome 5 are associated with serum IgE levels in Labrador retrievers.

Owczarek-Lipska M, Lauber B, Molitor V, Meury S, Kierczak M, Tengvall K, Webster MT, Jagannathan V, Schlotter Y, Willemse T, Hendricks A, Bergvall K, Hedhammar A, Andersson G, Lindblad-Toh K, Favrot C, Roosje P, Marti E, Leeb T - PLoS ONE (2012)

ELISA measurements of 15 immunological phenotypes depending on the genotype at SNP BICF2S2297212.The G-allele at this SNP was associated with the allergen-specific IgE response to A. siro. Note that dogs with the homozygous G/G genotype show a consistent trend for higher IgE levels across all measured antigens. Boxes represent the 25th and 75th percentile of the phenotypic distribution with the median indicated by a solid horizontal line. The whiskers indicate the minimum and maximum of the distributions. Outliers that are more than 1.5 times the interquartile range away from the median are shown as open circles. Abbreviations for allergens: Df, Dermatophagoides farinae; Dp, Dermatophagoides pteronyssinus; Tp, Tyrophagus putrescentiae; Ld, Lepidoglyphus destructor; As, Acarus siro; Aa, Alternaria alternate; Ch, Cladosporium herbarum; Af, Aspergillus fumigates; Ps, Penicillinum sp.; Cat, cat epithelium; Flea, flea saliva; Bg, Blattela germanica.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3376118&req=5

pone-0039176-g003: ELISA measurements of 15 immunological phenotypes depending on the genotype at SNP BICF2S2297212.The G-allele at this SNP was associated with the allergen-specific IgE response to A. siro. Note that dogs with the homozygous G/G genotype show a consistent trend for higher IgE levels across all measured antigens. Boxes represent the 25th and 75th percentile of the phenotypic distribution with the median indicated by a solid horizontal line. The whiskers indicate the minimum and maximum of the distributions. Outliers that are more than 1.5 times the interquartile range away from the median are shown as open circles. Abbreviations for allergens: Df, Dermatophagoides farinae; Dp, Dermatophagoides pteronyssinus; Tp, Tyrophagus putrescentiae; Ld, Lepidoglyphus destructor; As, Acarus siro; Aa, Alternaria alternate; Ch, Cladosporium herbarum; Af, Aspergillus fumigates; Ps, Penicillinum sp.; Cat, cat epithelium; Flea, flea saliva; Bg, Blattela germanica.
Mentions: We further analyzed whether there are any correlations between the A. siro-specific IgE responsiveness and the other studied traits. The best-associated SNP for this trait was BICF2S2297212 (Table 1). The A-allele at this SNP had a frequency of 7.8% and occurred almost exclusively in A. siro-specific IgE non-responsive dogs. When we grouped the dogs according to their genotypes at the associated SNP, we observed a consistent trend for dogs with the A-allele to have lower total and lower allergen-specific IgE levels with respect to all tested allergens compared to the dogs that were homozygous G/G. The genotype at this SNP had no visible correlation with the Dermatophagoides farinae-specific IgG1 or IgG4 levels (Figure 3).

Bottom Line: We identified a genome-wide significant association on CFA 5 with the antigen-specific IgE responsiveness to Acarus siro.We detected a second genome-wide significant association with respect to the antigen-specific IgE responsiveness to Tyrophagus putrescentiae at a different locus on chromosome 5.No obvious candidate gene for the regulation of IgE levels is located under the two association signals.

View Article: PubMed Central - PubMed

Affiliation: Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.

ABSTRACT
Crosslinking of immunoglobulin E antibodies (IgE) bound at the surface of mast cells and subsequent mediator release is considered the most important trigger for allergic reactions. Therefore, the genetic control of IgE levels is studied in the context of allergic diseases, such as asthma, atopic rhinitis, or atopic dermatitis (AD). We performed genome-wide association studies in 161 Labrador Retrievers with regard to total and allergen-specific immunoglobulin E (IgE) levels. We identified a genome-wide significant association on CFA 5 with the antigen-specific IgE responsiveness to Acarus siro. We detected a second genome-wide significant association with respect to the antigen-specific IgE responsiveness to Tyrophagus putrescentiae at a different locus on chromosome 5. A. siro and T. putrescentiae both belong to the family Acaridae and represent so-called storage or forage mites. These forage mites are discussed as major allergen sources in canine AD. No obvious candidate gene for the regulation of IgE levels is located under the two association signals. Therefore our studies offer a chance of identifying a novel mechanism controlling the host's IgE response.

Show MeSH
Related in: MedlinePlus