Glucose-6-Phosphate Dehydrogenase Deficiency is Associated with Cardiovascular Disease in U.S. Military Centers

Abstract

Glucose-6-phosphate dehydrogenase (G6PD) protects erythrocytes from oxidative stress and hemolysis; G6PD deficiency is the most prevalent enzymopathy. The United States military routinely performs tests to prevent exposing G6PD-deficient personnel to antimalarial drugs that might cause life-threatening hemolytic reactions. In addition, G6PD is a key determinant of vascular function, and its deficiency can lead to impaired nitric oxide production and greater vascular oxidant stress-precursors to atherosclerosis and cardiovascular disease. Using military medical records, we performed a retrospective, cross-sectional study to investigate whether deficient G6PD levels are associated with a higher prevalence of cardiovascular disease than are normal levels, and, if so, whether the relationship is independent of accepted cardiovascular risk factors. We analyzed the medical records of 737 individuals who had deficient G6PD levels and 16,601 who had normal levels. Everyone had been screened at U.S. military medical centers from August 2004 through December 2007. We evaluated our dependent variable (composite cardiovascular disease) at the individual level, and performed binary logistic regression of our independent variable (G6PD status) and control variables (modifiable cardiovascular risk factors). The adjusted odds ratio of 1.396 (95% CI, 1.044-1.867; P <0.05) indicated that G6PD-deficient individuals have 39.6% greater odds of developing cardiovascular disease than do those with normal levels. Early intervention may reduce the incidence of cardiovascular disease in military personnel and civilians who have deficient G6DP levels.

Keywords: Cardiovascular diseases/ethnology/enzymology/physiopathology; United States/epidemiology; delivery of health care; genetic predisposition to disease; glucose phosphate dehydrogenase deficiency/analysis/complications/diagnosis/epidemiology; mass screening; military medicine; retrospective studies; risk assessment; risk factors.

Fig. 1

The first reaction of the pentose phosphate pathway is the enzymatic dehydrogenation of glucose 6-phosphate by glucose 6-phosphate dehydrogenase (G6PD). ADP = adenosine diphosphate; ATP = adenosine triphosphate; eNOS = enzyme nitric oxide synthase; GSH = glutathione; GSSG = glutathione disulfide; NADP = nicotinamide adenine dinucleotide phosphate; NADP⁺ = reduced nicotinamide adenine dinucleotide phosphate; NO = nitric oxide