| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Outline of Final Research Achievements |
Several genome wide association studies have suggested that SLC2A9 gene plays an important role in hyperuricemia/gout. Around 80% of patients with hyperuricemia are reported to have decreased urinary excretion of urate. Because SLC2A9 is a urate reabsorptive transporter, we hypothesized that gain-of-function mutation and/or overexpression of SLC2A9 can explain low urinary excretion of urate in such patients. Genome sequence was obtained from a hyperuricemic patient and his father, who is also hyperuricemic, and his mother, who had normal urate levels. The patient had 2 mutations in SLC2A9 and these mutations did not affect urate transport activity. Two rare variants in the enhancer region of SLC2A9, existing both in the patient’s and his father’s, but not in his mother’s genome showed increased promoter activity in luciferase assay. We knocked in these 2 variants into HepG2 cells by CRISPR-Cas9 but the cells failed to show increased expression of SLC2A9.
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