G6PD deficiency and the cardiovascular system

G6PD deficiency and the cardiovascular system

G6PD deficiency and the cardiovascular system: Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme in the cytoplasm which acts in the pentose phosphate pathway of metabolism which helps in the formation of NADPH (reduced form of nicotinamide adenine dinucleotide phosphate). NADPH is an important defense against oxidative stress. NADPH is also required for fatty acid and cholesterol synthesis. There is a theory that G6PD deficiency reduces risk for cardiovascular diseases. In 1998 a study by Pierluigi Cocco, Pierfelice Todde, Susanna Fornera, Maria Bonaria Manca, Pierina Manca and Ana Rosa Sias evaluated this aspect [1]. They evaluated about 1800 males who been detected to have G6PD deficiency by an official population screening program. It was found that mortality from cardiovascular diseases was about half of what was expected. The decrease in deaths was mostly explained by reduced deaths due to coronary artery disease and cerebrovascular disease. The earlier hypothesis was that G6PD deficient individuals may be less susceptible to cardiovascular disease because there wouldn’t be enough NADPH for intima cell proliferation during atheroma proliferation.

Another study by Antonio Pinna, Ciriaco Carru, Giuliana Solinas, Angelo Zinellu and Francesco Carta evaluated the relation between G6PD deficiency and retinal vein occlusion [2]. They concluded that the frequency of G6PD deficiency in patients with retinal vein occlusion was lower than that expected in that population with a high incidence of the condition.

Contrary to these observations, Mohit Jain, Lei Cui, Daniel A Brenner, Bo Wang, Diane E Handy, Jane A Leopold, Joseph Loscalzo, Carl S Apstein and Ronglih Liao [3] based on experimental studies suggest that G6PD is an essential myocardial enzyme for protecting against oxidative stress induced dysfunction during reperfusion following ischemia.

Marjolein Drent, Anton P Gorgels and Aalt Bast in a letter to the editor of Circulation Research [4] proposed that a case of cardiac failure in a person with sarcoidosis was associated with G6PD deficiency. They thought that G6PD deficiency may cause vulnerability to oxidative damage and cardiac failure. With this in mind they treated the person with carvedilol, a beta blocker with antioxidant properties, in addition to conventional medications for heart failure. The good response to therapy was also considered to be a pointer to their hypothesis. Only future studies will clarify which of these hypotheses are really true.

References

  1. Pierluigi Cocco, Pierfelice Todde, Susanna Fornera, Maria Bonaria Manca, Pierina Manca, and Ana Rosa Sias. Mortality in a Cohort of Men Expressing the Glucose-6-Phosphate Dehydrogenase Deficiency. Blood, 1998;91: 706-709.
  2. Antonio Pinna, Ciriaco Carru, Giuliana Solinas, Angelo Zinellu, Francesco Carta. Glucose-6-phosphate dehydrogenase deficiency in retinal vein occlusion. Invest Ophthalmol Vis Sci. 2007;48:2747-52.
  3. Mohit Jain, Lei Cui, Daniel A Brenner, Bo Wang, Diane E Handy, Jane A Leopold, Joseph Loscalzo, Carl S Apstein, Ronglih Liao. Increased myocardial dysfunction after ischemia-reperfusion in mice lacking glucose-6-phosphate dehydrogenase. Circulation. 2004 ;109:898-903.
  4. Marjolein Drent, Anton P Gorgels, Aalt Bast. Cardiac failure associated with G6PD deficiency. Circ Res. 2003 Oct 17;93(8):e75.