A collaborative research team has shown that genetic mutations in a gaint protein also impact heart function in healthy people. The heart may be healthy initially but it reacts to this genetic stress. And when an additional stressor occurs, the heart may bucome unhealthy. The study appears in Nature Genetics.
Scientists have known for some time that genetic mutations in a protein called titin can cause dilated cardiomyopathy (DCM), a common disease of the heart muscle. DCM -- a common cause of heart failure -- can also contributes to irregular heartbeats, blood clots or sudden death. This inherited heart condition can affect people of all ages including children, but is most common in men ages 20 to 60. According to estimates, 1 in 250 people will develop this disease. However, many people that carry titin mutations exhibit no sign of disease.
To identify why this occurs, an international research team led by National Heart Centre Singapore has made extensive and in-depth research on titin mutations. Results show that mutations in titin also have an impact on the heart function in healthy people.
Titin is a gaint protein, and it is encoded by the TTN gene in humans. This protein is a key component in the assembly and functioning of vertebrates straited muscles. It functions as a molecular spring which is responsible for the passive elasticity of muscle. In patients with DCM, titin mutations are significantly associated with the disease.
To unravel the effects of titin mutations on heart function, the research team, led by Nicole Tee and Stuart A Cook from National Heart Centre Singapore, investigated 2,495 DCM patients and 1,409 healthy participants. They also created rat models to understand the roles of titin mutations at the molecular level. You can find various proteins, such as Titin and Recombinant Dpp4.
The results showed that the genetic mutations affect the titin protein production, which influences the heart. Healthy people with titin mutations live in a compensated state and the main heart pumping chamber is slightly bigger. Using various genomic methods, the researchers discovered that the RNA that is produced from the actual titin allele which carries the mutation, is degraded in the cells of the heart.
The study extends the understanding of DCM, and provides new insights into the impact of titin mutations in healthy people. It would improve the diagnosis and treatment of DCM. Future research will be focused on the genetic and environmental factors that make people carrying titin mutations more likely to develop heart disease.
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