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DIFFERENTIAL BLOOD GENE EXPRESSION PATTERNS FOR NYHA
CLASSIFICATION AND BNP LEVELS IN HEART FAILURE
A.S. Go1,2, J. Ma3, M. Chandra1, G. Gee4, C.C. Liew3,5
1
Kaiser Permanente of Northern California, Oakland, CA, USA, 2University of
California, San Francisco, San Francisco, CA, USA, 3GeneNews Limited,
Richmond,ON,Canada, 4Kaiser Permanente Oakland Medical Center, Oakland, CA,
USA, 5Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
Objectives. We examined blood gene expression patterns associated with clinical severity
and B-type natriuretic peptide (BNP) levels in heart failure (HF). Background.
Determining HF severity is challenging. New York Heart Association (NYHA)
classification and BNP are often used but are limited. Blood gene expression patterns
may provide further insights into disease severity, but patterns associated with NYHA
class and BNP are unknown.
Methods. Among 97 adults with and without HF, we measured BNP and extracted total
RNA from peripheral leukocytes. Microarray hybridization was performed using
GeneChip U133Plus2 (Affymetrix) to examine gene expression profiles.
Results. We analyzed 20 controls (mean BNP:53), 20 NYHA-I (mean BNP:183), 20
NYHA-II (mean BNP:477), 30 NYHA-III (mean BNP:545) and 7 NYHA-IV (mean
BNP:434). Overall, 489 genes were differentially regulated between controls, NYHA I/II
and NYHA III/IV (P<0.005), with many involved in energy metabolism (eg, galactose,
glycerolipid) and immune response (eg, NF-kB signalling) pathways. A total of 1160
genes were correlated with BNP (P<0.005) and were primarily related to immune
responses and regulation, (eg, IL-10 and Toll-like receptor signalling). Expression
patterns associated with NYHA class appeared distinct from BNP with only 90
overlapping genes.
Conclusions. Blood gene expression differs for clinical severity and BNP in HF. BNP
was associated with activation of blood genes involved in immune responses and
regulation, while clinical severity showed broader effects on blood expression patterns.
Our findings reinforce BNP’s limited correlation with clinical severity and the need to
determine the value of blood gene expression profiling in optimizing HF management
and outcomes.