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Potential Contribution of SIM2 and ETS2 Functional Polymorphisms in Down Syndrome Associated Malignancies

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Title Potential Contribution of SIM2 and ETS2 Functional Polymorphisms in Down Syndrome Associated Malignancies
 
Creator Chatterjee, Arpita
Dutta, Samikshan
Mukherjee, Sanjit
Mukherjee, Nupur
Dutta, Avirup
Mukherjee, Ashis
Sinha, Swagata
Panda, Chinmay Kumar
Chaudhuri, Keya
Roy, Ananda L
Mukhopadhyay, Kanchan
 
Subject Molecular & Human Genetics
 
Description Proper expression and functioning of transcription factors (TFs) are essential for regulation of different
traits and thus could be crucial for the development of complex diseases. Subjects with Down syndrome (DS) have
a higher incidence of acute lymphoblastic leukemia (ALL) while solid tumors, like breast cancer (BC) and oral cancer
(OC), show rare incidences. Triplication of the human chromosome 21 in DS is associated with altered genetic
dosage of different TFs. V-ets erythroblastosis virus E26 oncogene homolog 2 (ETS2) and Single Minded 2 (SIM2) are
two such TFs that regulate several downstream genes involved in developmental and neurological pathways. Here
we studied functional genetic polymorphisms (fSNP) in ETS2 and SIM2 encoding genes in a group of patients and
control subjects to better understand association of these variants with DS phenotypes.We employed an in silico approach to identify potential target pathways of ETS2 and SIM2. fSNPs in genes encoding for these two TFs were identified using available databases. Selected sites were genotyped in individuals with DS, their parents, ALL, BC, OC as well as ethnically matched control individuals. We further analyzed these data by population-based statistical methods.Allelic/genotypic association analysis showed significant (P < 0.03) differences of rs2070530, rs1051476, rs11254, rs711 for DS subjects compared to control. rs711 also exhibited significantly different genotypic distribution pattern in parents of DS probands (P < 0.02) and BC patients (P < 0.02). Interaction analysis revealed independent main effect of rs711 in all the groups, while rs11254 exhibited independent main effect in DS subjects only. High entropy values were noticed for rs461155 in the solid tumor groups. Significant interactive effects of rs2070531 with rs1051475, rs1051476, rs11254 were observed in all the groups except DS.
We infer from the present investigation that the difference in frequencies of fSNPs and their independent as well as interactive effects may be the cause for altered expression of SIM2 and ETS2 in DS and malignant groups, which affects different downstream biological pathways. Thus, altered expression of SIM2 and ETS2 could be one of the reasons for variable occurrence of different malignant conditions in DS.
 
Publisher BioMed Central
 
Date 2013
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1806/1/BMC_MEDICAL_GENETICS__14_____Article_Number_12;2013[7].pdf
Chatterjee, Arpita and Dutta, Samikshan and Mukherjee, Sanjit and Mukherjee, Nupur and Dutta, Avirup and Mukherjee, Ashis and Sinha, Swagata and Panda, Chinmay Kumar and Chaudhuri, Keya and Roy, Ananda L and Mukhopadhyay, Kanchan (2013) Potential Contribution of SIM2 and ETS2 Functional Polymorphisms in Down Syndrome Associated Malignancies. BMC Medical Genetics, 14 (12).
 
Relation http://dx.doi.org/10.1186/1471-2350-14-12
http://www.eprints.iicb.res.in/1806/