DNA microarray analysis of chromosomal susceptibility regions to identify candidate genes for allergic disease: a pilot study.
OBJECTIVE
To examine whether DNA microarray analysis of chromosomal susceptibility regions for allergy can help to identify candidate genes.


METHODS
Nasal biopsies were obtained from 23 patients with allergic rhinitis and 12 healthy controls. RNA was extracted from the biopsies and pooled into three patient and three control pools. These were then analysed in duplicate with DNA microarrays containing 12626 genes. Candidate genes were further examined in nasal biopsies (real-time polymerase chain reaction) and blood samples (single nucleotide polymorphisms) from other patients with allergic rhinitis and from controls.


RESULTS
A total of 37 differentially expressed genes were identified according to criteria involving both the size and consistency of the gene expression levels. The chromosomal location of these genes was compared with the chromosomal susceptibility regions for allergic disease. Using a statistical method, five genes were identified in these regions, including serine protease inhibitor, Kazal type, 5 (SPINK5) and HLA-DRB2. The relevance of these genes was examined in other patients with allergic rhinitis and in controls; none of the genes were differentially expressed in nasal biopsies. Moreover, no association between allergic rhinitis and SPINK5 polymorphisms was found, at either the genotype or haplotype level.


CONCLUSIONS
DNA microarray analysis of chromosomal susceptibility regions did not lead to identification of candidate genes that could be validated in a new material. However, because gene polymorphisms may cause differential gene expression, further studies, including validation data, are needed to examine this approach.
Benson
Mikael
M
Laboratory for Clinical and Experimental Allergy Research, Department of Oto-rhino-laryngology Malmö University Hospital, Lund University, Malmö, Sweden. mikael.benson@vgregion.se
Svensson
Per-Arne
PA
Adner
Mikael
M
Carén
Helena
H
Carlsson
Björn
B
Carlsson
Lena M S
LM
Martinsson
Tommy
T
Rudemo
Mats
M
Cardell
Lars Olaf
LO
D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002875:Chromosomes / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D015802:HLA-DR2 Antigen / Q000235:genetics / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010865:Pilot Projects; D011110:Polymorphism, Genetic / Q000235:genetics; D053491:Proteinase Inhibitory Proteins, Secretory; D020133:Reverse Transcriptase Polymerase Chain Reaction; D048348:Reverse Transcription / Q000235:genetics; D012221:Rhinitis, Allergic, Perennial / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D000074163:Serine Peptidase Inhibitor Kazal-Type 5
D002352:Carrier Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D015802:HLA-DR2 Antigen; D053491:Proteinase Inhibitory Proteins, Secretory; C120650:SPINK5 protein, human; D000074163:Serine Peptidase Inhibitor Kazal-Type 5