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KMID : 1225720140060060496
Allergy, Asthma & Immunology Research : AAIR
2014 Volume.6 No. 6 p.496 ~ p.503
Novel genes in Human Asthma Based on a Mouse Model of Allergic Airway Inflammation and Human Investigations
Temesi Gergely

Virag Viktor
Hadadi Eva
Ungvari Ildiko
Fodor Lili E
Bikov Andras
Nagy Adrienne
Galffy Gabriella
Tamasi Lilla
Horvath Ildiko
Kiss Andras
Hullam Gabor
Gezsi Andras
Sarkozy Peter
Antal Peter
Buzas Edit
Szalai Csaba
Abstract
Purpose: Based on a previous gene expression study in a mouse model of asthma, we selected 60 candidate genes and investigated their possible roles in human asthma.

Methods: In these candidate genes, 90 SNPs were genotyped using MassARRAY technology from 311 asthmatic children and 360 healthy controls of the Hungarian (Caucasian) population. Moreover, gene expression levels were measured by RT PCR in the induced sputum of 13 asthmatics and 10 control individuals. t-tests, chi-square tests, and logistic regression were carried out in order to assess associations of SNP frequency and expression level with asthma. Permutation tests were performed to account for multiple hypothesis testing.

Results: The frequency of 4 SNPs in 2 genes differed significantly between asthmatic and control subjects: SNPs rs2240572, rs2240571, rs3735222 in gene SCIN, and rs32588 in gene PPARGC1B. Carriers of the minor alleles had reduced risk of asthma with an odds ratio of 0.64 (0.51-0.80; P=7¡¿10-5) in SCIN and 0.56 (0.42-0.76; P=1.2¡¿10-4) in PPARGC1B. The expression levels of SCIN, PPARGC1B and ITLN1 genes were significantly lower in the sputum of asthmatics.

Conclusions: Three potentially novel asthma-associated genes were identified based on mouse experiments and human studies.
KEYWORD
Asthma, child, genetic association studies, gene expression, sputum, disease model, animal
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