Comprehensive evaluation of genetic variation in S100A7 suggests an association with the occurrence of allergic rhinitis.
BACKGROUND
S100A7 is a calcium-binding protein with chemotactic and antimicrobial properties. S100A7 protein levels are decreased in nasal lavage fluid from individuals with ongoing allergic rhinitis, suggesting a role for S100A7 in allergic airway inflammation. The aims of this study were to describe genetic variation in S100A7 and search for associations between this variation and allergic rhinitis.


METHODS
Peripheral blood was collected from 184 atopic patients with a history of pollen-induced allergic rhinitis and 378 non-atopic individuals, all of Swedish origin. DNA was extracted and the S100A7 gene was resequenced in a subset of 47 randomly selected atopic individuals. Nine polymorphisms were genotyped in 184 atopic and 378 non-atopic individuals and subsequently investigated for associations with allergic rhinitis as well as skin prick test results. Haplotypes were estimated and compared in the two groups.


RESULTS
Thirteen polymorphisms were identified in S100A7, of which 7 were previously undescribed. rs3014837 (G/C), which gives rise to an Asp --> Glu amino acid shift, had significantly increased minor allele frequency in atopic individuals. The major haplotype, containing the major allele at all sites, was more common in non-atopic individuals, while the haplotype containing the minor allele at rs3014837 was equally more common among the atopic individuals. Additionally, heterozygotes at this site had significantly higher scores in skin prick tests for 9 out of 11 tested allergens, compared to homozygotes.


CONCLUSIONS
This is the first study describing genetic variation, associated with allergy, in S100A7. The results indicate that rs3014837 is linked to allergic rhinitis in our Swedish population and render S100A7 a strong candidate for further investigations regarding its role in allergic inflammation.
Bryborn
Malin
M
Laboratory of Clinical and Experimental Allergy Research, Department of Otorhinolaryngology, Malmö University Hospital, LundUniversity, Malmö, Sweden. malin.bryborn@med.lu.se
Halldén
Christer
C
Säll
Torbjörn
T
Adner
Mikael
M
Cardell
Lars Olaf
LO
D000328:Adult; D000368:Aged; D000485:Allergens / Q000276:immunology*; D052179:Antigens, Plant / Q000276:immunology*; D029662:Betula / Q000276:immunology*; D002135:Calcium-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007428:Intradermal Tests; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D006109:Poaceae / Q000276:immunology*; D011058:Pollen / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide; D006255:Rhinitis, Allergic, Seasonal / Q000235:genetics* / Q000276:immunology; D012307:Risk Factors; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; D013548:Sweden
D000485:Allergens; D052179:Antigens, Plant; D002135:Calcium-Binding Proteins; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human