Novel genes in Human Asthma Based on a Mouse Model of Allergic Airway Inflammation and Human Investigations.
OBJECTIVE
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.
Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
Gergely
G
Temesi
Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
Viktor
V
Virág
Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary. ; Department of Cardiovascular Science, University of Sheffield, Sheffield, UK.
Eva
E
Hadadi
Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
Ildikó
I
Ungvári
Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
Lili E
LE
Fodor
Department of Pulmonology, Semmelweis University, Budapest, Hungary.
András
A
Bikov
Heim, Pal Children Hospital, Budapest, Hungary.
Adrienne
A
Nagy
Department of Pulmonology, Semmelweis University, Budapest, Hungary.
Gabriella
G
Gálffy
Department of Pulmonology, Semmelweis University, Budapest, Hungary.
Lilla
L
Tamási
Department of Pulmonology, Semmelweis University, Budapest, Hungary. ; Ministry of National Resources, Budapest, Hungary.
Ildikó
I
Horváth
Heim, Pal Children Hospital, Budapest, Hungary.
András
A
Kiss
Department of Measurement and Information Systems, University of Technology and Economics, Budapest, Hungary.
Gábor
G
Hullám
Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
András
A
Gézsi
Department of Measurement and Information Systems, University of Technology and Economics, Budapest, Hungary.
Péter
P
Sárközy
Department of Measurement and Information Systems, University of Technology and Economics, Budapest, Hungary.
Péter
P
Antal
Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
Edit
E
Buzás
Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary. ; Heim, Pal Children Hospital, Budapest, Hungary. ; Csertex Research Laboratory, Budapest, Hungary.
Csaba
C
Szalai
Asthma; animal; child; disease model; genetic association studies, gene expression; sputum