P.13.2 A prostaglandin D2 metabolite is elevated in the urine samples of patients with Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disease caused by muscle dystrophin deficiency. Disease mechanisms caused by primary dystrophin deficiency are not well elucidated. Recently, urinary 11,15-dioxo-9α-hydroxy-, 2,3,4,5-tetranorprostan-1,20-dioic acid (tetranor PGDM) was shown to be a major metabolite of prostaglandin D2 (PGD2) and reflects to its biosynthesis. Here, the hypothesis that PGD2-mediated inflammation is involved in the pathology of DMD was examined by measuring tetranor PGDM in urine of DMD patients. We measured tetranor PGDM in the patients’ urine samples using LC–MS/MS. One hundred seventeen genetically confirmed DMD patients from 4 to 15years of age were enrolled in this study and their first morning urines were obtained at 191 points. Age matched 71 male controls were recruited from healthy relatives or volunteers and first morning urines were obtained at 79 points. The urinary tetranor PGDM levels were 3.08±0.15 and 6.90±0.35ng/mg creatinine (mean ±SE) in 79 control and 191 DMD points, respectively. The mean level in the DMD points was approximately 2.2-times higher than in the control points (p <0.05). Especially, urinary tetranor PGDM level increases with age of DMD patients. It stayed nearly 1.5 times higher than control until 7years old but surged at the age of 8 to a significantly higher level. On the other hand, the level in controls does not show no significant difference between ages. Urinary tetranor PGDM levels were elevated in DMD patients and became higher with advancing age. It was suggested that PGD2-mediated inflammation should be taken into consideration in understanding the pathology of DMD, especially in older patients. [ABSTRACT FROM AUTHOR]