Allergy Asthma Immunol Res.  2014 Nov;6(6):496-503. 10.4168/aair.2014.6.6.496.

Novel genes in Human Asthma Based on a Mouse Model of Allergic Airway Inflammation and Human Investigations

• Temesi G
• Virag V
• Hadadi E
• Ungvari I
• Fodor LE
• Bikov A
• Nagy A
• Galffy G
• Tamasi L
• Horvath I
• Kiss A
• Hullam G
• Gezsi A
• Sarkozy P
• Antal P
• Buzas E
• Szalai C

• KMID: 2260171
• DOI: http://doi.org/10.4168/aair.2014.6.6.496

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=7x10(-5)) in SCIN and 0.56 (0.42-0.76; P=1.2x10(-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

MeSH Terms

Alleles
Animals
Asthma*
Child
Gene Expression
Humans
Inflammation*
Logistic Models
Mice*
Odds Ratio
Polymerase Chain Reaction
Polymorphism, Single Nucleotide
Sputum

Figure

• 

  Figure Gene expression level changes between cases and controls in human induced sputum samples and ovalbumin-induced mouse model: all the 3 investigated genes (SCIN, PPARGC1B, ITLN1) had significant expression level change, but their expressions were higher in the mouse model (marked with darker columns) and lower in human asthmatics (marked with brighter columns) than in the controls. For statistical significance of the sputum samples, please refer to Table 5.

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