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Two‐dimensional protein electrophoresis and multiple hypothesis testing to detect potential serum protein biomarkers in children with fetal alcohol syndrome
Author(s) -
Robinson Mary K.,
Myrick James E.,
Henderson L. Omar,
Coles Claire D.,
Powell Mary K.,
Orr Geoffrey A.,
Lemkin Peter F.
Publication year - 1995
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/elps.11501601195
Subject(s) - fetus , fetal alcohol syndrome , chromatography , prenatal alcohol exposure , alcohol , gel electrophoresis of proteins , fetal alcohol , chemistry , medicine , biology , biochemistry , polyacrylamide gel electrophoresis , genetics , pregnancy , enzyme
Fetal alcohol syndrome (FAS) surveillance and intervention efforts are hampered by the lack of a specific biochemical test for diagnosis of the syndrome. Based on the hypothesis that abnormalities in growth and development (key features of FAS) involve altered protein metabolism, we analyzed serum proteins by two‐dimensional gel electrophoresis and image analysis to search for potential protein biomarkers of FAS. Serum samples from 12 participants in whom FAS had been diagnosed and 8 sex‐ and age‐matched participants whose mothers did not consume alcohol were analyzed in duplicate to determine whether the integrated intensities of matched proteins are significantly altered in children with FAS. Multiple hypothesis testing on 34 of the gels consisting of more than 1700 spots per gel revealed 21 proteins that we classified as potential protein biomarkers of FAS on the basis of significant t ‐test differences at p < 0.02. We classified 8 of the proteins as candidate biomarkers on the basis of significant concentration differences between case and control subjects at p < 0.01. One of the proteins is clearly an isoform of retinol binding protein; two appear in the area of the gel where alcohol dehydrogenase is expected to appear; one appears to be an isoform of alpha‐1‐antitrypsin; three appear to be isoforms of the beta‐chain of haptoglobin; three may be forms of immunoglobulin light chains; and several others have not been associated with known proteins. No single protein differentiated all case subjects from control subjects, but stepwise canonical discriminant analyses revealed four groups of spots that distinguished between FAS case and control subjects with no misclassifications. Because of the small number of samples analyzed, we have not positively identified the proteins. It will be necessary to confirm our observations using additional samples before identifying each protein.