Search for sarcoidosis candidate genes by integration of data from genomic, transcriptomic and proteomic studies.
BACKGROUND
The search for gene candidates in multifactorial diseases such as sarcoidosis can be based on the integration of linkage association data, gene expression data, and protein profile data from genomic, transcriptomic and proteomic studies, respectively.


METHODS
In this study we performed a literature-based search for studies reporting such data, followed by integration of collected information. Different databases were examined--Medline, HugGE Navigator, ArrayExpress and Gene Expression Omnibus (GEO). Candidate genes were defined as genes which were reported in at least 2 different types of omics studies. Genes previously investigated in sarcoidosis were excluded from further analyses.


RESULTS
We identified 177 genes associated with sarcoidosis as potential new candidate genes. Subsequently, 9 gene candidates identified to overlap in 2 different types of studies (genomic, transcriptomic and/or proteomic) were consistently reported in at least 3 studies: SERPINB1, FABP4, S100A8, HBEGF, IL7R, LRIG1, PTPN23, DPM2 and NUP214. These genes are involved in regulation of immune response, cellular proliferation, apoptosis, inhibition of protease activity, lipid metabolism. Exact biological functions of HBEGF, LRIG1, PTPN23, DPM2 and NUP214 remain to be completely elucidated.


CONCLUSIONS
We propose 9 candidate genes: SERPINB1, FABP4, S100A8, HBEGF, IL7R, LRIG1, PTPN23, DPM2 and NUP214, as genes with high potential for association with sarcoidosis.
Maver
Ales
A
Department of Obstetrics and Gynecology, Institute of Medical Genetics, University Medical Centre Ljubljana, Ljubljana, Slovenia.
Medica
Igor
I
Peterlin
Borut
B
D040501:Calgranulin A / Q000235:genetics; D030541:Databases, Genetic; D050556:Fatty Acid-Binding Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D023281:Genomics; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008364:Mannosyltransferases / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics; D028861:Nuclear Pore Complex Proteins / Q000235:genetics; D040081:Protein Array Analysis; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000235:genetics; D040901:Proteomics; D020395:Receptors, Interleukin-7 / Q000235:genetics; D012507:Sarcoidosis / Q000235:genetics*; D015843:Serpins / Q000235:genetics
D040501:Calgranulin A; C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; C484445:LRIG1 protein, human; D008562:Membrane Glycoproteins; C085914:NUP214 protein, human; D028861:Nuclear Pore Complex Proteins; D020395:Receptors, Interleukin-7; D015843:Serpins; C075177:SERPINB1 protein, human; C115077:DPM2 protein, human; D008364:Mannosyltransferases; C114102:PTPN23 protein, human; D054558:Protein Tyrosine Phosphatases, Non-Receptor