Background: In this study, the expression of hypoxanthine-guanine phosphoribosyl transferase (HPRT) in Down's syndrome patients with gout (DS/G) was determined, and possible underlying mechanisms of gout were characterized using proteomic tools.
Methods: Serum was obtained from DS/G, healthy controls and gout patients (without DS), recruited from the rheumatology clinic. Baseline enzyme assays were recorded and RT-PCR used to identify HPRT gene expression. 2-D electrophoresis and mass spectrometry were utilized to determine a plausible explanation concerning the mechanisms leading to increased uric acid levels in DS patients.
Results: Two DS patients were diagnosed with gouty arthritis. Their HPRT enzyme activity was slightly lower than that of normal controls. HPRT expression was also slightly decreased in DS/G patients compared with controls. Serum protein profiles of these two DS/G patients revealed that haptoglobin alpha chain and apolipoprotein A1 (ApoA1) were both significantly down-regulated. Protein expression was validated by immunoblot.
Conclusion: Our results revealed that low levels of haptoglobin in the two DS/G patients were related to renal dysfunction may have affected uric acid excretion and caused gout. However, decreased ApoA1 revealed a positive correlation between defective lipid metabolism and gouty arthritis in DS/G patients.