SOD2 Gene Variation Associated with Susceptibility to PAH, Chinese Study Shows

José Lopes, PhD avatar

by José Lopes, PhD |

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A variation in the gene sequence of superoxide dismutase 2 (SOD2) is associated with a susceptibility to pulmonary arterial hypertension (PAH), new research from China shows.

SOD2 is an antioxidant enzyme that transforms the superoxide radical into hydrogen peroxide and oxygen.

The study, “Role for Functional SOD2 Polymorphism in Pulmonary Arterial Hypertension in a Chinese Population,” was published in the International Journal of Environmental Research and Public Health.

Oxidative stress plays an essential role in PAH. Abnormal expression of oxidative genes and the presence of reactive oxygen species (ROS) in vascular cells were found in pulmonary tissues in PAH. Elevated levels of ROS are associated with vascular dysregulation, leading to smooth muscle hypercontractility, elevated pulmonary arterial pressure, and right ventricular heart failure.

Single nucleotide polymorphisms (SNP, variations within the DNA sequence when a single nucleotide – the building block of DNA – differs between members of a species or a pair of alleles in an individual) of SOD2 have been found to influence the susceptibility to cancer.

In particular, the C (for the DNA base cytosine) allele of rs4880, an SOD2 SNP that leads to an amino acid substitution, is associated with lower SOD2 activity than the TT genotype (T for tyrosine). Therefore, the researchers hypothesized that rs4880 could influence the expression of SOD2 and be associated with PAH.

The research team was led by Baoli Zhu, from the Department of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Control and Prevention in China.

In a case-control study including 460 patients and 530 healthy controls from China, patients with TC + CC genotypes in rs4880 showed increased susceptibility and worsened clinical features of PAH, compared to TT controls.

And, in in vitro experiments, the researchers observed that the C allele was associated with decreased levels of SOD2.

Limitations of the study include the relatively small sample size and the possibility that other regulation mechanisms may have influenced SOD2 levels.

Nonetheless, results show that the rs4880 polymorphism decreases the levels of SOD2.

“There is significant association between SOD rs4880 polymorphism and the PAH susceptibility, and this polymorphism influenced PAH susceptibility by altering the expression of SOD2,” the team concluded.

A Conversation With Rare Disease Advocates