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BMC Medical Genetics

, 14:12

Genetic epidemiology and genetic associations

Abstract

BackgroundProper 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.

MethodsWe 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.

ResultsAllelic-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.

ConclusionsWe 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.

KeywordsSIM2 ETS2 Down syndrome Breast cancer Oral cancer Acute lymphoblastic leukemia Electronic supplementary materialThe online version of this article doi:10.1186-1471-2350-14-12 contains supplementary material, which is available to authorized users.

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Autor: Arpita Chatterjee - Samikshan Dutta - Sanjit Mukherjee - Nupur Mukherjee - Avirup Dutta - Ashis Mukherjee - Swagata Sinha -

Fuente: https://link.springer.com/







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