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

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.

journal_name

Immunogenetics

journal_title

Immunogenetics

authors

Perin P,Potočnik U

doi

10.1007/s00251-013-0755-0

subject

Has Abstract

pub_date

2014-03-01 00:00:00

pages

143-51

issue

3

eissn

0093-7711

issn

1432-1211

journal_volume

66

pub_type

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