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Polymorphisms in recent GWA identified asthma genes CA10, SGK493, and CTNNA3 are associated with disease severity and treatment response in childhood asthma

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Abstract

Recent genome-wide association studies (GWAs) have identified several new genetic risk factors for asthma; however, their influence on disease behavior and treatment response is still unclear. The aim of our study was the association analysis of the most significant single nucleotide polymorphisms (SNPs) recently reported by GWAs in different phenotypes of childhood asthma and analysis of correlation between these SNPs and clinical parameters. We have genotyped 288 children with asthma and 276 healthy controls. We provided here first replication of bivariate associations between CA10 (p = 0.001) and SGK493 (p = 0.011) with asthma. In addition, we have identified new correlation between SNPs in CA10, SGK493, and CTNNA3 with asthma behavior and glucocorticoid treatment response. Asthma patients who carried G allele in SNP rs967676 in gene CA10 were associated with more pronounced airway obstruction, higher bronchial hyper-reactivity, and increased inflammation. Higher bronchial hyper-reactivity was also associated with C allele in SNP rs1440095 in gene SGK493 but only in nonatopic asthmatics. In addition, we found that patients who carried at least one T allele in SNP rs1786929 in CTNNA3 (p = 0.022) and atopic patients who carried at least one G allele in SNP rs967676 in gene CA10 (p = 0.034) had higher increase in pulmonary function after glucocorticoid therapy. Our results suggest genetic heterogeneity between atopic and nonatopic asthma. We provided further evidence that treatment response in childhood asthma is genetically predisposed, and we report here two novel SNPs in genes CA10 and CTNNA3 as potential pharmacogenetic biomarkers that could be used in personalized treatment in childhood asthma.

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Acknowledgments

This study was supported by the Slovenian research agency. Many thanks to Dr. Vojko Berce and Dr. Maja Kavalar for patients’ samples and clinical data. Special thanks to Alojz Tapajner for his help and advices in statistical analysis.

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Authors and Affiliations

  1. Faculty of Medicine, Center for Human Molecular Genetics and Pharmacogenomics, University of Maribor, Slomškov trg 15, 2000, Maribor, Slovenia

    Petra Perin & Uroš Potočnik

  2. Faculty of Chemistry and Chemical Technology, Laboratory for Biochemistry Molecular Biology and Genomics, University of Maribor, Smetanova 17, 2000, Maribor, Slovenia

    Petra Perin & Uroš Potočnik

  3. Faculty of Health Science, University of Maribor, Žitna ulica 22, 2000, Maribor, Slovenia

    Petra Perin

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  1. Petra Perin
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Correspondence to Uroš Potočnik.

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Supplementary Table 1

Conditions for PCR-RFLP reactions and fragment size after completion of test. (DOCX 16 kb)

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Perin, P., Potočnik, U. Polymorphisms in recent GWA identified asthma genes CA10, SGK493, and CTNNA3 are associated with disease severity and treatment response in childhood asthma. Immunogenetics 66, 143–151 (2014). https://doi.org/10.1007/s00251-013-0755-0

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