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http://purl.uniprot.org/citations/22679008http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22679008http://www.w3.org/2000/01/rdf-schema#comment"

Rationale

An increased tricuspid regurgitation jet velocity (TRV > 2.5 m/s) and pulmonary hypertension defined by right heart catheterization both independently confer increased mortality in sickle cell disease (SCD).

Objectives

We explored the usefulness of peripheral blood mononuclear cell-derived gene signatures as biomarkers for an elevated TRV in SCD.

Methods

Twenty-seven patients with SCD underwent echocardiography and peripheral blood mononuclear cell isolation for expression profiling and 112 patients with SCD were genotyped for single-nucleotide polymorphisms.

Measurements and main results

Genome-wide gene and miRNA expression profiles were correlated against TRV, yielding 631 transcripts and 12 miRNAs. Support vector machine analysis identified a 10-gene signature including GALNT13 (encoding polypeptide N-acetylgalactosaminyltransferase 13) that discriminates patients with and without increased TRV with 100% accuracy. This finding was then validated in a cohort of patients with SCD without (n = 10) and with pulmonary hypertension (n = 10, 90% accuracy). Increased TRV-related miRNAs revealed strong in silico binding predictions of miR-301a to GALNT13 corroborated by microarray analyses demonstrating an inverse correlation between their expression. A genetic association study comparing patients with an elevated (n = 49) versus normal (n = 63) TRV revealed five significant single-nucleotide polymorphisms within GALNT13 (P < 0.005), four trans-acting (P < 2.1 × 10(-7)) and one cis-acting (P = 0.6 × 10(-4)) expression quantitative trait locus upstream of the adenosine-A2B receptor gene (ADORA2B).

Conclusions

These studies validate the clinical usefulness of genomic signatures as potential biomarkers and highlight ADORA2B and GALNT13 as potential candidate genes in SCD-associated elevated TRV."xsd:string
http://purl.uniprot.org/citations/22679008http://purl.org/dc/terms/identifier"doi:10.1164/rccm.201201-0057oc"xsd:string
http://purl.uniprot.org/citations/22679008http://purl.uniprot.org/core/author"Huang Y."xsd:string
http://purl.uniprot.org/citations/22679008http://purl.uniprot.org/core/author"Zhang W."xsd:string
http://purl.uniprot.org/citations/22679008http://purl.uniprot.org/core/author"Mu W."xsd:string
http://purl.uniprot.org/citations/22679008http://purl.uniprot.org/core/author"Zhou T."xsd:string
http://purl.uniprot.org/citations/22679008http://purl.uniprot.org/core/author"Yuan J.X."xsd:string
http://purl.uniprot.org/citations/22679008http://purl.uniprot.org/core/author"Raghavachari N."xsd:string
http://purl.uniprot.org/citations/22679008http://purl.uniprot.org/core/author"Ahmad H."xsd:string
http://purl.uniprot.org/citations/22679008http://purl.uniprot.org/core/author"Turner K."xsd:string
http://purl.uniprot.org/citations/22679008http://purl.uniprot.org/core/author"Gordeuk V.R."xsd:string
http://purl.uniprot.org/citations/22679008http://purl.uniprot.org/core/author"Garcia J.G."xsd:string
http://purl.uniprot.org/citations/22679008http://purl.uniprot.org/core/author"Wade M.S."xsd:string
http://purl.uniprot.org/citations/22679008http://purl.uniprot.org/core/author"Kato G.J."xsd:string
http://purl.uniprot.org/citations/22679008http://purl.uniprot.org/core/author"Patel A.R."xsd:string
http://purl.uniprot.org/citations/22679008http://purl.uniprot.org/core/author"Lang R.M."xsd:string
http://purl.uniprot.org/citations/22679008http://purl.uniprot.org/core/author"Desai A.A."xsd:string
http://purl.uniprot.org/citations/22679008http://purl.uniprot.org/core/author"Artz N."xsd:string
http://purl.uniprot.org/citations/22679008http://purl.uniprot.org/core/author"Machado R.F."xsd:string
http://purl.uniprot.org/citations/22679008http://purl.uniprot.org/core/author"Peters-Lawrence M.H."xsd:string
http://purl.uniprot.org/citations/22679008http://purl.uniprot.org/core/author"Thiruvoipati T."xsd:string
http://purl.uniprot.org/citations/22679008http://purl.uniprot.org/core/author"Trevino S."xsd:string
http://purl.uniprot.org/citations/22679008http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22679008http://purl.uniprot.org/core/name"Am J Respir Crit Care Med"xsd:string
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