Association between polymorphisms in serine protease inhibitor, kazal type 5 and asthma phenotypes in a large German population sample

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Abstract
Background Atopic diseases are characterized by immunoglobulin E (IgE)‐mediated immune responses towards common allergens, many of which are proteases. Recently it has been suggested that a proteinase inhibitor gene, SPINK5, which is located on chromosome 5q31, may play a role in the pathogenesis of atopic diseases. Objective We investigated the association between the polymorphism G1258A leading to a putative amino acid change (Glu420Lys) in serine protease inhibitor, kazal type 5 (SPINK5) and phenotypes of atopic diseases in a large general population sample of German children. Methods Parental questionnaires were used and children underwent skin prick testing, pulmonary function testing and bronchial challenge. Blood was collected for serum IgE measurements and DNA extraction. In total, 1161 children were genotyped for the SPINK5 Glu420Lys polymorphism and association studies were performed. Results A significant association between SPINK5 420Lys and the development of asthma was observed (OR 1.77; 95%CI: 1.02–3.06, P=0.041 for 420Lys homocygotes). Atopic carriers of SPINK5 420Lys showed an increased risk for asthma and asthma symptoms (OR 2.06; 95%CI: 1.01–4.20, P=0.047). When children with a combination of asthma and atopic dermatitis were compared with normal controls, the SPINK5 420Lys genotype was more prevalent in the disease group (OR 4.56; 95%CI: 1.370–15.12, P=0.007). No association between SPINK5 420Lys genotypes and total serum IgE levels, skin prick test (SPT) reactivity or atopic dermatitis was observed. Conclusion These results suggest that SPINK5 Glu420Lys polymorphism may be associated with certain asthma phenotypes characterized by the concomitant expression of asthma and atopic dermatitis or SPT reactivity.