Screening and preliminary validation of new protein markers in maternal serum for early diagnosis of Down syndrome

Abstract

Objective To assess the clinical application values of the protein markers associated with Down syndrome （DS）in maternal serum which were screened and identified. Methods Seven maternal serum samples with DS fetus （DS group） and 7 maternal serum samples with normal fetus （control group） in the second trimester were separated by two-dimensional gel electrophoresis （2-DE）.The differentinal expression profile of proteome in maternal serum from DS group was established.The differentially expressed proteins were screened by mass spectrometry （MS） and some proteins were verified by Western blotting （WB）. Results Twenty-nine proteins were discovered to be differentially expressed by more than 1.5 folds in maternal serum from DS group, among which 19 proteins were up-regulated and 10 proteins were down- regulated.Eight proteins displayed 2 or more folds changes in maternal serum from DS group were identified by MS and possibly matched with 12 proteins in Ameracan National Center of Biotchnology Information （NCBI） protein sequence database, such as dGTPase and Beta2-Glycoprotein I （β2-GPI）, etc.The results of WB showed that the mean a values of dGTPase and β2-GPI were 21 567.0±3009.4 and 22 097.0±3958.9 in the DS group, 3957.7±250.9 and 1799.7±105.5 in the control group respectively, which presented that the expression of dGTPase and β2-GPI significantly increased in DS group (t′dGTPase=-17.66，t′β2-GPI=-14.83，P＜0.0001). Conclusions 2-DE and MS are effective methods for preliminary identification of protein markers associated with DS in maternal serum.dGTPase and β2-GPI verified by WB laid a solid fundation for further screening new biologic markers for early diaglosis of DS.(Chin J Lab Med， 2012,35：328-332) Key words: Down syndrome; Blood proteins; Biological markers; Proteomics