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Objective: Primary gout has been associated with single-nucleotide polymorphisms (SNP) in several tubular urate transporter genes. No study has assessed the association of reabsorption and secretion urate transporter gene SNP with gout in a single cohort of documented primary patients with gout carefully subclassified as normoexcretors or underexcretors., Methods: Three reabsorption SNP (SLC22A12/URAT1, SLC2A9/GLUT9, and SLC22A11/OAT4) and 2 secretion transporter SNP (SLC17A1/NPT1 and ABCG2/BRCP) were studied in 104 patients with primary gout and in 300 control subjects. The patients were subclassified into normoexcretors and underexcretors according to their serum and 24-h urinary uric acid levels under strict conditions of dietary control., Results: Compared with control subjects, patients with gout showed different allele distributions of the 5 SNP analyzed. However, the diagnosis of underexcretor was only positively associated with the presence of the T allele of URAT1 rs11231825, the G allele of GLUT9 rs16890979, and the A allele of ABCG2 rs2231142. The association of the A allele of ABCG2 rs2231142 in normoexcretors was 10 times higher than in underexcretors. The C allele of NPT1 rs1165196 was only significantly associated with gout in patients with normal uric acid excretion., Conclusion: Gout with uric acid underexcretion is associated with transporter gene SNP related mainly to tubular reabsorption, whereas uric acid normoexcretion is associated only with tubular secretion SNP. This finding supports the concept of distinctive mechanisms to account for hyperuricemia in patients with gout with reduced or normal uric acid excretion.

Background and Objectives: Pharmacologic urate lowering therapy (ULT), at full maintenance doses, has been associated with acute gout arthritis (in up to 80% of patients). The American College of Rheumatology has recently advocated gradually titrating the maintenance dose upward to chosen serum urate target. Few studies have examined the efficacy and safety of a ULT in primary gout., Patients and Methods: The ULT regimen examined included allopurinol (50 mg/day, with increases of 50 mg/month up to 300 mg/day) and colchicine, as prophylaxis to prevent acute gouty attacks. The efficacy and safety of this regimen was examined in 42 patients in whom allopurinol was withheld for ≥3 months and restarted after this assessment and followed up for 12 months. The efficacy and safety of the ULT regimen was related to the serum urate decrease and to the incidence of acute gout flares, respectively., Results: Fifty-nine patients (mean age 59 years, 56 men) with primary gout received the gradually titrated ULT regimen. Baseline serum urate was (mean±SD) 8.4±0.8 mg/dL. At 3, 6, 9, and 12 months serum urate fell by a mean of 1.8, 2.5, 2.7, and 2.5 mg/dL, respectively (p<0.001). A serum urate level<6.0 mg/dL was achieved by 38/59 (64%) patients. During the 12 months following the start of the ULT we documented 10 acute arthritis episodes (17% of patients)., Conclusions: A gradually titrated hypouricemic regimen for 6 months in patients with primary gout appears to be effective and safe.

Background and Objectives: Primary gout has traditionally been associated with obesity, arterial hypertension, and abnormal lipid and glucose homeostasis, but we do not know the prevalence of these vascular risk factors in patients with primary gout from a Mediterranean country., Patients and Method: All patients with primary gout and 2 or more acute arthritis episodes documented by a physician were selected for the study. The diagnosis of MS required ≥3 criteria (ATP III). Patients were classified in two groups: decreased (underexcretors) and normal (normoexcretors) uric acid excretion related to serum urate levels., Results: One hundred and four patients (mean age, 59 years; 100 males) with primary gout were included in the study. MS was diagnosed in 38 subjects (37%). The most frequent triad defining MS was an increased waist circumference, blood pressure, and trygliceride levels. The prevalence of type 2 diabetes mellitus (T2D) was significantly higher in patients with the MS (21/38, 55%) as compared with subjects without the MS (3/66, 5%; p<0.001). Mean serum urate level in patients with and without MS was identical (8.1 mg/dL), but mean 24-hour uric acid excretion was significantly lower in the former than in the latter (444±110 mg/24-hour/1,73 m2 versus 546±221 mg/day/1,73 m2; p=0.009)., Conclusions: The condition of the MS occurs in about one-third of the patients with primary gout. Increased waist circumference, blood pressure, and triglycerides levels is the most frequent MS triad. Diminished urinary uric acid excretion is more severe in gout patients with the MS.