Source: International Congress 2014 – Genes and environment in asthma and COPD
Disease area: Airway diseases

Abstract

Background Calcium homeostasis contributes to increased airway smooth muscle contraction, a core feature of asthma. Several candidate genes exist affecting calcium homeostasis. Two of these genes interact functionally, ATP2A2 and ORMDL3 (Cantero-Recasens G et al Hum Mol Gen 2010;19:111-121).Aim To study interactions between SNPs in ATP2A2 and ORMDL3 in asthma and their association with gene expression in lung tissue. Methods SNPs tagging ATP2A2(n=3) and ORMDL3(n=12) were selected in a birth cohort (PIAMA: 111 asthma; 468 controls) and adult asthmatics(775 asthma; 468 controls). Genetic associations of SNPs with asthma and gene expression were tested using univariate and interaction models.Results Seven SNPs in ORMDL3 were significantly associated with asthma. Rs3026445 in ATP2A2 and 6 ORMDL3 SNPs had significant interactions in childhood asthma only. All ORMDL3 SNPs changed ORMDL3 gene-expression. Rs3026445 was not associated with ATP2A2 gene expression. Significant interactions between ATP2A2 and ORMDL3 SNPs were found on gene expression of both ATP2A2 and ORMDL3(table1).Conclusion We found no association of ATP2A2 SNPs with asthma, but significant genetic interaction between ATP2A2 and ORMDL3 with asthma and gene expression in lung tissue. Thus, SNPs without univariate association with asthma or gene expression, may still be important since their modifying potential in associations of SNPs in another gene with these outcomes.



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M. Nieuwenhuis, J. Vonk, M. van den Berge, Y. Bossé, D. Nickle, G. Koppelman, D. Postma (Groningen, Netherlands; Quèbec, Canada; Seattle, United States Of America). Genetic interaction between ATP2A2 and ORMDL3, a calcium handling origin of asthma. Eur Respir J 2014; 44: Suppl. 58, 2928

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