Author/Editor		Borovečki, F; Lovrečić, L; Zhou, J; Jeong, H; Then, F; Rosas, HD; Hersch, SM; Hogarth, P; Bouzou, B; Jensen, RV; Krainc, D
Title		Genome-wide expression profiling of human blood reveals biomarkers for Huntington's disease
Type		članek
Source		Proc Natl Acad Sci U S A
Vol. and No.		Letnik 102, št. 31
Publication year		2005
Volume		str. 11023-8
Language		eng
Abstract		Huntingtons disease (HD) is an autosomal dominant disorder caused by an expansion of glutamine repeats in ubiquitously distributed huntingtin protein. Recent studies have shown that mutant huntingtin interferes with the function of widely expressed transcription factors, suggesting that gene expression may be altered in a variety of tissues in HD, including peripheral blood. Affymetrix and Amersham Biosciences oligonucleotide microarrays were used to analyze global gene expression in blood samples of HD patients and matched controls. We identified 322 mRNAs that showed significantly altered expression in HD blood samples, compared with controls (p<0.0005), on two different microarray platforms. A subest of up-regulated mRNAs selected from this group was able to distinguish controls, presymptomatic individuals carrving the HD mutation, and symptomatic HD patients. In addition, early presymptomatic subjects showed gene expression profiles similar to those of controls, whereas late presymptomatic subject showed altered expression that resembled that of symptomatic HD patients. These elevated mRNAs were significantly reduced in HD patients involved in a dose-finding study of the histone deacetylase inhibitor sodium phenylbutyrate. Furthermore, expression of the marker genes was significantly up-regulated in postmortem HD caudate, suggesting that alterations in blood mRNAs may reflect disease mechanisms observed in HD brain. In conclusion, we identified changes in blood mRNAs that clearly distinguish HD patients from controls. These alterations in mRNA expression correlate with disease progression and response to experimental treatment. Such markers may provide clues to the state of HD and may be of predictive value in clinical trials.
Descriptors		HUNTINGTON'S DISEASE GENETIC MARKERS GENOME, HUMAN GENE EXPRESSION PHENYLBUTYRATES SEX FACTORS ADULT MIDDLE AGE RNA, MESSENGER BASE SEQUENCE BRAIN DNA PRIMERS ENZYME INHIBITORS HISTONE DEACETYLASE CASE-CONTROL STUDIES