Pulmonary hypertension associated with Whipple disease.
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ABSTRACT:
SUBMITTER: Baloira A
PROVIDER: S-EPMC9487411 | biostudies-literature | 2014 Dec
REPOSITORIES: biostudies-literature
Publications
Pulmonary hypertension associated with Whipple disease.
Baloira Adolfo A Núñez Marta M Tumbeiro Manuel M Parente-Lamelas Isaura I Bastos María M Gutiérrez Mario M
European respiratory review : an official journal of the European Respiratory Society 20141201 134
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Project description:BackgroundPulmonary hypertension (PH) is a severe complication of sarcoidosis in a minority of patients. Several genetic defects are known to cause hereditary or sporadic PH, but whether variants in PH-associated genes are also involved in sarcoidosis-associated PH (SAPH) is unknown.Methods40 patients with SAPH were individually matched to 40 sarcoidosis patients without PH (SA). Whole exome sequencing was performed to identify rare genetic variants in a diagnostic PH gene panel of 13 genes. Additionally, an exploratory analysis was performed to search for other genes of interest. From 572 genes biologically involved in PH pathways, genes were selected in which at least 15% of the SAPH patients and no more than 5% of patients without PH carried a rare variant.ResultsIn the diagnostic PH gene panel, 20 different rare variants, of which 18 cause an amino-acid substitution, were detected in 23 patients: 14 SAPH patients carried a variant, as compared to 5 SA patients without PH (p = 0.018). Most variants were of yet unknown significance. The exploratory approach yielded five genes of interest. First, the NOTCH3 gene that was previously linked to PH, and furthermore PDE6B, GUCY2F, COL5A1, and MMP21.ConclusionsThe increased frequency of variants in PH genes in SAPH suggests a mechanism whereby the presence of such a genetic variant in a patient may increase risk for the development of PH in the context of pulmonary sarcoidosis. Replication and studies into the functionality of the variants are required for further understanding the pathogenesis of SAPH.
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