• Childhood Kidney Diseases
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• v.10 no.1
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• pp.65-71
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• 2006

Idiopathic renal hypouricemia is a disorder characterized by impaired urate handling in the renal tubules. Most patients with hypouricemia are asymptomatic and are found incidentally, but the condition is known to be at high risk for exercise-induced acute renal failure or urolithiasis. URAT1 protein encoded by SLC22A12 gene has been identified recently as a urate/anion exchanger in the human kidney. Inactivation mutations in SLC22A12 gene have been shown to cause renal idiopathic hypouricemia. We experienced a 3-year-old boy who presented with persistent orange-colored urine since infancy. His urine contained many uric acid crystals, while the serum showed hypouricemia(0.7 mg/dL). The fractional excretion of uric acid was increased to 41.7%. SLC22a12 gene analysis revealed W258X homozygote alleles. Renal hypouricemia must be included in the differential diagnosis of red-urine and SLC22A12 gene analysis is recommended in idiopathic renal hypouricemia.

• Childhood Kidney Diseases
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• v.25 no.1
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• pp.44-48
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• 2021

Idiopathic renal hypouricemia (iRHUC) is a rare hereditary disease caused by a defect in urate handling of renal tubules. Type 1 renal hypouricemia (RHUC1) is diagnosed with confirmation of a mutation in SLC22A12 gene which encodes a renal urate-anion exchanger (URAT1). The majority of iRHUC patients are asymptomatic, especially during childhood, and thus many cases go undiagnosed or they are diagnosed late in older age with complications of hematuria, renal stones, or acute kidney injury (AKI). We report a case of a 7-year-old boy with subtle symptoms such as general weakness and dizziness and revealed hypouricemia and incidental nephrolithiasis. Homozygous mutations were detected in the SLC22A12 (c.774G>A) by molecular analysis. The present case suggests that fractional excretion of uric acid (FEUA) screening could be better followed by the coincidental discovery of hypouricemia, to prevent conflicting complications of iRHUC, even with normal urine uric acid to creatinine ratio (U_UA/U_Cr), and sequential genetic analysis if needed.

• Childhood Kidney Diseases
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• v.16 no.2
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• pp.121-125
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• 2012

Gitelman syndrome is an autosomal recessive renal tubular disorder characterized by hypokalemic metabolic alkalosis, and it is distinguished from Batter syndrome by hypomagnesemia and hypocalciuria. This disorder is caused by mutation in SLC12A3 gene which encodes thiazide-sensitive $Na^+-Cl^-$cotransporter (NCCT) which is expressed in the apical membrane of cells, lining distal convoluted tubule. A 8-year old boy who presented with Rolandic epilepsy, and horseshoe kidney accidentally showed clinical features of metabolic alkalosis, hypokalemia, hypocalciuria without hypomagnesemia. So we identified a heterozygote mutation and an abnormal splicing in the SLC12A3 gene, encoding NCCT. The mutation was detected in the exon 15 and 22 of SLC12A3 gene.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.4
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• pp.319-325
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• 2015

Among solute carrier proteins, the organic anion transporters (OATs) play an important role for the elimination or reabsorption of endogenous and exogenous negatively charged anionic compounds. Among OATs, SLC22A9 (hOAT7) transports estrone sulfate with high affinity. The net decrease of estrogen, especially in post-menopausal women induces rapid bone loss. The present study was performed to search the SNP within exon regions of SLC22A9 in Korean females with osteoporosis. Fifty healthy controls and 50 osteoporosis patients were screened for the genetic polymorphism in the coding region of SLC22A9 using GC-clamped PCR and denaturing gradient gel electrophoresis (DGGE). Six SNPs were found on the SLC22A9 gene from Korean women with/without osteoporosis. The SNPs were located as follows: two SNPs in the osteoporosis group (A645G and T1277C), three SNPs in the control group (G1449T, C1467T and C1487T) and one SNP in both the osteoporosis and control groups (G767A). The G767A, T1277C and C1487T SNPs result in an amino acid substitution, from synonymous vs nonsynonymous substitution arginine to glutamine (R256Q), phenylalanine to serine (F426S) and proline to leucine (P496L), respectively. The Km values and Vmax of the wild type, R256Q, P496L and F426S were 8.84, 8.87, 9.83 and $12.74{\mu}M$, and 1.97, 1.96, 2.06 and 1.55 pmol/oocyte/h, respectively. The present study demonstrates that the SLC22A9 variant F426S is causing inter-individual variation that is leading to the differences in transport of the steroid sulfate conjugate (estrone sulfate) and, therefore this could be used as a marker for certain disease including osteoporosis.

• Journal of Nutrition and Health
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• v.50 no.1
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• pp.32-40
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• 2017

Purpose: Obesogenic environments in children, in particular excessive intake of sodium, generate hypertension, which is a major risk factor for chronic diseases. Methods: In all, 725 children, 379 boys and 373 girls, aged 8~9 years were recruited from seven elementary schools in Kuro-ku, Seoul. To evaluate whether or not obesity risk was modulated by salt-sensitive genes, Solute Carrier Familiy 12 member 3 (SLC12A3) was used as the target. After children were assigned into obese (BMI > 85 percentile) or non-obese groups, anthropometry, blood biochemistry, and dietary intakes were measured according to the genotypes GG (wild) or GA+AA (hetero+mutant). Results: Without gender differences, high TG and low HDLc were detected in the obese group compared to the non-obese group. Regardless of obesity, weight gain and blood pressure (BP) increased in the SLC12A3 GA+AA genotype rather than in the GG type. HDLc was associated with obesity risk without genotype difference. Odd ratios for risk of obesity were 15.57 (95% CI 2.192~110.654), 22.84 (95% CI 1.565~333.469), and 9.32 (95%CI 1.262~68.817) in boys and girls with GA+AA genotypes as sodium intake increased above 4,000 mg/day. Dietary calcium, sodium, folate, and vit C were associated with obesity risk according to gender or genotype differences. Since high folate intake reduced obesity risk in only boys with GG type. Risk for overweight and obesity increased in boys with GA+AA genotypes and dietary habits with high sodium and cholesterol and low folate. Conclusion: The A allele of SLC12A3 rs11643718 was sensitive to development of obesity in children as sodium intake increased.

• Clinical and Experimental Pediatrics
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• v.50 no.5
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• pp.489-492
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• 2007

Idiopathic renal hypouricemia is a disorder characterized by impaired urate handling in the renal tubules. This disease usually produces no symptoms, but hematuria, uric acid nephrolithiasis or acute renal failure may develop. A defect in the SLC22A12 gene, which encodes the human urate transporter, is the known major cause of this disorder. We describe a 10-month-old boy with idiopathic renal hypouricemia. He was diagnosed with transient pseudohypoaldosteronism at admission, but hypouricemia was accidentally found through follow-up study. By gene analysis, his diagnosis was confirmed to idiopathic renal hypouricemia. In addition, we report a mutation in the human urate transporter 1 (hURAT1) gene identified in his family.

• Journal of Korean Medicine for Obesity Research
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• v.22 no.2
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• pp.93-101
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• 2022

Objectives: This study aimed to observe the anti-diabetic effect and underlying mechanisms of Galgunhwanggumhwangryun-tang (GHH; Gegen-Qinlian-decoction) in the C2C12 myotubes. Methods: GHH (1.0 mg/ml) or metformin (0.75 mM) or insulin (100 nM) were treated in C2C12 myotubes after 4 days differentiation. The glucose uptake was assessed by 2-[N-(7-160 nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose uptake by C2C12 cells. The expression of adenosine monophosphate-activated protein kinase (AMPK) and phosphorylation AMPK (pAMPK) were measured by western blot. We also evaluated gene expression of glucose transporter type 4 (Slc2a4, formerly known as GLUT4), glucokinase (Gk), carnitine palmitoyltransferase IA (Cpt1a), nuclear respiratory factors 1 (Nrf1), mitochondrial transcription factor A (Tfam), and peroxisome proliferator-activated receptor γ coactivator 1α (Ppargc1a) by quantitative real-time polymerase chain reaction. Results: GHH promoted glucose uptake in C2C12 myotubes. The expression of AMPK protein, which plays an essential role in glucose metabolism, was increased by treatment with GHH. GHH treatment tended to increase gene expression of Slc2a4, Gk, and Nrf1 but was not statistically significant. However, GHH significantly improved Tfam and Ppargc1a gene expression in C2C12 myotubes. Conclusions: In summary, GHH treatment promoted glucose uptake in C2C12 myotubes. We suggest that these effects are associated with increased gene expression involved in mitochondrial biosynthesis and oxidative phosphorylation, such as Tfam and Ppargc1a, and increased expression of AMPK protein.