The tet-methylcytosine-dioxygenase-2 (TET2) gene may affect the onset and progression of pulmonary arterial hypertension (PAH), according to a new study published in CJC Open.
“TET2 may work as a modifier gene,” the authors wrote.
They also identified a new TET2 variant called p.Ser1039Leu in 3 patients with PAH from Japan. Previous work has identified new TET2 gene variants in patients with PAH, but in the present study, a team of researchers wanted to investigate the frequency of TET2 variants in these patients.
Masaharu Kataoka, MD, from the Department of Cardiology at the Keio University School of Medicine in Tokyo, Japan led the team in conducting whole-exome sequencing in 145 patients with idiopathic or hereditary PAH.
PAH can be idiopathic or occur with no known cause. It can be hereditary and passed down in families, induced by drugs or toxins, or associated with other conditions such as connective tissue disorders, portal hypertension, congenital heart disease schistosomiasis, or HIV infection.
Read more about PAH etiology
The whole-exome sequencing approach identified 3 patients with a heterozygous missense germline mutation (c.3116C>T, p.Ser1039Leu) located on about 270 base pairs upstream of the catalytic core domain in the TET2 gene. The researchers reported that these 3 patients had to be treated with combination therapy of vasodilators that included continuous prostacyclin infusion.
“The allele frequency [of the new variant] is 0.15% in [genome aggregation database], and 0.2% among 3554 Japanese general population,” the researchers wrote.
They concluded that TET2 variants are present in patients with PAH regardless of ethnic background.
The exact role of the TET2 protein is not known but it is thought to be involved in DNA methylation. The lack of functional TET2 causes myeloid tumorigenesis. Therefore, the protein seems to act as a tumor suppressor.
Hiraide T, Suzuki H, Shinya Y, et al. TET2 variants in Japanese patients with pulmonary arterial hypertension. CJC Open. Published online November 26, 2021. doi:10.1016/j.cjco.2021.11.008