DNMT3B Gene May Cause Pulmonary Hypertension, PAH Development

Recently, Pulmonary Hypertension News shared some burgeoning medical news: that the DNMT3B gene has now been linked to the development of pulmonary hypertension (PH) and a rare form of chronic high blood pressure called pulmonary arterial hypertension (PAH) in a rat study. Check out the full study findings published in Science Advances.


According to GeneCards, the DNMT3B gene is a protein coding gene that plays a role in DNA methylation, which is important for development:

CpG methylation is an epigenetic modification that is important for embryonic development, imprinting, and X-chromosome inactivation. This gene encodes a DNA methyltransferase which is thought to function in de novo methylation, rather than maintenance methylation.

DNA methylation is an epigenetic mechanism. What Is Epigenetics explains that the process:

occurs by the addition of a methyl (CH3) group to DNA, thereby often modifying the function of the genes and affecting gene expression.

This process can activate, silence, or inhibit gene expression. For a while, researchers have questioned whether DNA methylation causes the development of PH. So researchers from the Tongji University School of Medicine used rat models of pulmonary hypertension to understand how this process, and DNMT enzymes produced by the gene, impacted PH development.

The Research

To begin, researchers induced hypoxia in the rats, as well as injected them with monocrotaline (MCT). Together, these contributed to low oxygen, high blood pressure, hypertension, and thicker heart tissue, all key components of PH. After testing these rat models after 3 weeks, researchers determined that these rats (MCT) experienced a 1.8x increase in DNA methylation than the control group. Those who experienced hypoxia had a 1.4x increase in methylation.

Next, researchers began studying which specific DNMT genes could cause heightened DNA methylation. After testing, they narrowed this down to the DNMT3B gene. Gene expression was high in the rat models. Similarly, prior research suggests that heightened DNMT3B activity can be found in patients with PAH at a significantly higher level than control groups (up to 24x higher).
Next, researchers created a rat model of PH with DNMT3B deficiency. Within a month of being injected with MCT, these rats had much higher rates of thickened heart tissue and high blood pressure. When treated in a hyperbaric oxygen chamber to induce hypoxia, DNMT3B-deficient rats also showed increased thickening compared to controls.
Finally, researchers wanted to test whether increased DNMT3B activity could inhibit PH. They delivered a functional DNMT3B gene to both control and gene deficient rats. Ultimately, researchers determined that heightened DNMT3B expression not only reduced high blood pressure, but protecting against the thickening of smooth muscle cells, heart tissue, and blood vessels.

Pulmonary Arterial Hypertension (PAH)

As a chronic and progressive form of high blood pressure, pulmonary arterial hypertension (PAH) causes the thickening or hardening of pulmonary arteries. As these arteries narrow or thicken, it becomes difficult to move the blood through or receive oxygen. Thus, the heart begins working harder and harder to achieve this, causing heart damage. Females are 2x more likely to develop PAH than males. It typically affects those between ages 30 and 60. An estimated 500-1,000 new cases of PAH are diagnosed each year.

While PAH is most commonly caused by BMPR2 gene mutations, it can also be caused by HIV, lung or liver disease, autoimmune diseases, and congestive heart failure. Symptoms include:

  • Chest pain
  • Shortness of breath, especially during exercise or other activity
  • Swelling in the lower extremities
  • Fatigue
  • Heart palpitations
  • Blue lips or fingers
  • Dizziness
  • Fainting
Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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