Gene Expression in BMPR2 Mutation Carriers and Pulmonary Arterial Hypertension
Author Information
Author(s): James West, Joy Cogan, Mark Geraci, Linda Robinson, John Newman, John A Phillips, Kirk Lane, Barbara Meyrick, Jim Loyd
Primary Institution: Vanderbilt University Medical Center
Hypothesis
Modifier genes contribute to the clinical expression of pulmonary arterial hypertension (PAH) in BMPR2 mutation carriers.
Conclusion
Alterations in gene expression pathways related to proliferation, GTP signaling, and stress response are correlated with disease status in BMPR2 mutation carriers.
Supporting Evidence
- CYP1B1 expression was significantly lower in female PAH patients compared to unaffected carriers.
- Gene expression differences were observed in pathways related to stress response and actin organization.
- The study used patient-derived lymphoblastoid cell lines to minimize confounding effects from disease and drugs.
Takeaway
Some people with a gene mutation that can cause a serious lung disease don't get sick, and this study looks at why that happens by checking their genes.
Methodology
B-cells were isolated and cultured from familial PAH patients and their relatives to examine gene expression differences using Affymetrix arrays and quantitative RT-PCR.
Potential Biases
The study may underestimate the false discovery rate due to differences in relation between unaffected and affected carriers.
Limitations
The study design resulted in age mismatches between groups and potential biases due to the use of B-cells instead of disease-relevant cells.
Participant Demographics
The study included 20 individuals from one family, with 5 affected by PAH and 7 unaffected carriers, aged 15 to 88 years.
Statistical Information
P-Value
p<0.05
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
Want to read the original?
Access the complete publication on the publisher's website