PMID- 23625463
OWN - NLM
STAT- MEDLINE
DCOM- 20131022
LR  - 20211021
IS  - 1432-1440 (Electronic)
IS  - 0946-2716 (Linking)
VI  - 91
IP  - 8
DP  - 2013 Aug
TI  - Gene expression profiling and association studies implicate the neuregulin 
      signaling pathway in Behcet's disease susceptibility.
PG  - 1013-23
LID - 10.1007/s00109-013-1022-4 [doi]
AB  - Behcet's disease (BD) is a complex disease with genetic and environmental risk 
      factors implicated in its etiology; however, its pathophysiology is poorly 
      understood. To decipher BD's genetic underpinnings, we combined gene expression 
      profiling with pathway analysis and association studies. We compared the gene 
      expression profiles in peripheral blood mononuclear cells (PBMCs) of 15 patients 
      and 14 matched controls using Affymetrix microarrays and found that the 
      neuregulin signaling pathway was over-represented among the differentially 
      expressed genes. The Epiregulin (EREG), Amphiregulin (AREG), and Neuregulin-1 
      (NRG1) genes of this pathway stand out as they are also among the top 
      differentially expressed genes. Twelve haplotype tagging SNPs at the EREG-AREG 
      locus and 15 SNPs in NRG1 found associated in at least one published BD 
      genome-wide association study were tested for association with BD in a dataset of 
      976 Iranian patients and 839 controls. We found a novel association with BD for 
      the rs6845297 SNP located downstream of EREG, and replicated three associations 
      at NRG1 (rs4489285, rs383632, and rs1462891). Multifactor dimensionality 
      reduction analysis indicated the existence of epistatic interactions between EREG 
      and NRG1 variants. EREG-AREG and NRG1, which are members of the epidermal growth 
      factor (EGF) family, seem to modulate BD susceptibility through main effects and 
      gene-gene interactions. These association findings support a role for the 
      EGF/ErbB signaling pathway in BD pathogenesis that warrants further investigation 
      and highlight the importance of combining genetic and genomic approaches to 
      dissect the genetic architecture of complex diseases.
FAU - Xavier, Joana M
AU  - Xavier JM
AD  - Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 
      Av. Prof. Egas Moniz, Edificio Egas Moniz, 1649-028 Lisboa, Portugal.
FAU - Krug, Tiago
AU  - Krug T
FAU - Davatchi, Fereydoun
AU  - Davatchi F
FAU - Shahram, Farhad
AU  - Shahram F
FAU - Fonseca, Benedita V
AU  - Fonseca BV
FAU - Jesus, Gorete
AU  - Jesus G
FAU - Barcelos, Filipe
AU  - Barcelos F
FAU - Vedes, Joana
AU  - Vedes J
FAU - Salgado, Manuel
AU  - Salgado M
FAU - Abdollahi, Bahar Sadeghi
AU  - Abdollahi BS
FAU - Nadji, Abdolhadi
AU  - Nadji A
FAU - Moraes-Fontes, Maria Francisca
AU  - Moraes-Fontes MF
FAU - Shafiee, Niloofar Mojarad
AU  - Shafiee NM
FAU - Ghaderibarmi, Fahmida
AU  - Ghaderibarmi F
FAU - Vaz Patto, Jose
AU  - Vaz Patto J
FAU - Crespo, Jorge
AU  - Crespo J
FAU - Oliveira, Sofia A
AU  - Oliveira SA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130427
PL  - Germany
TA  - J Mol Med (Berl)
JT  - Journal of molecular medicine (Berlin, Germany)
JID - 9504370
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (EGF Family of Proteins)
RN  - 0 (EREG protein, human)
RN  - 0 (Epiregulin)
RN  - 0 (Glycoproteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (NRG1 protein, human)
RN  - 0 (Neuregulin-1)
RN  - 62229-50-9 (Epidermal Growth Factor)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Amphiregulin
MH  - Behcet Syndrome/*genetics/metabolism
MH  - EGF Family of Proteins
MH  - Epidermal Growth Factor/*genetics/metabolism
MH  - Epiregulin
MH  - Female
MH  - Gene Expression Profiling
MH  - Genome-Wide Association Study
MH  - Glycoproteins/*genetics/metabolism
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/*genetics/metabolism
MH  - Leukocytes, Mononuclear/metabolism
MH  - Male
MH  - Middle Aged
MH  - Neuregulin-1/*genetics/metabolism
MH  - Oligonucleotide Array Sequence Analysis
MH  - Polymorphism, Single Nucleotide
MH  - Signal Transduction
MH  - Young Adult
EDAT- 2013/04/30 06:00
MHDA- 2013/10/23 06:00
CRDT- 2013/04/30 06:00
PHST- 2012/12/10 00:00 [received]
PHST- 2013/03/07 00:00 [accepted]
PHST- 2013/02/01 00:00 [revised]
PHST- 2013/04/30 06:00 [entrez]
PHST- 2013/04/30 06:00 [pubmed]
PHST- 2013/10/23 06:00 [medline]
AID - 10.1007/s00109-013-1022-4 [doi]
PST - ppublish
SO  - J Mol Med (Berl). 2013 Aug;91(8):1013-23. doi: 10.1007/s00109-013-1022-4. Epub 
      2013 Apr 27.