Joo Hoon Lee

University of Ulsan, Urusan, Ulsan, South Korea

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Publications (37)53.73 Total impact

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    ABSTRACT: Nephronophthisis 13 (NPHP 13) is associated with mutations in the WDR19 gene, which encodes for a protein in the intraflagellar transport complex. Herein, we describe six additional cases accompanied by Caroli syndrome or disease. Targeted exome sequencing covering 96 ciliopathy-related genes was performed for 48 unrelated Korean patients with a clinical suspicion of NPHP. Mutations were confirmed by Sanger sequencing. We evaluated the expression of WDR19 in the biopsied kidney by immunohistochemistry in patients and controls. We detected three (3/48, 6.3 %) unrelated index cases with WDR19 mutations. One of the cases involved two siblings with the same mutation. Later, we detected an additional index case with a similar phenotype of kidney and liver involvement by Sanger sequencing of WDR19. The p.R1178Q mutation was common in all patients. All of the six affected patients from four families progressed to chronic kidney disease. Of note, all six patients had Caroli syndrome or disease. Immunohistochemistry for WDR19 showed localized expression along the luminal borders of the renal tubular epithelium in controls, whereas it showed diffuse cytoplasmic staining in the affected patients. Caroli disease is a major extra-renal phenotype associated with mutations in WDR19 in the Korean population. In this study, we visually validated the expression pattern of mutant WDR19 protein in the kidneys of NPHP 13 patients. More data are needed to identify the true frequency of p.R1178Q. Functional studies including transfection assay will provide solid grounds for the pathogenicity of each mutation.
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    ABSTRACT: Atypical hemolytic uremic syndrome (aHUS) is a rare disease with a genetic predisposition. Few studies have evaluated the disease in Asian population. We studied a Korean pediatric cohort to delineate the clinical characteristics and genotypes. A multicenter cohort of 51 Korean children with aHUS was screened for mutations by targeted exome sequencing covering 46 complement related genes. Anti-complement-factor-H autoantibodies (anti-CFH) titers were measured. Multiplex ligation dependent probe amplification assay was performed to detect deletions in the complement factor-H related protein genes (CFHRs). We grouped the patients according to the etiology and compared the clinical features using the Mann-Whitney U test and chi-square test. Fifteen patients (Group A, 29.7%) had anti-CFH and mutations were detected in 11(Group B, 21.6%) patients, including one with combined mutations. Remaining 25(Group C, 49.0%) were neither-positive. Anti-CFH-association was more frequent than the world-wide prevalence. Group A showed older onset age than Group B, although did not significantly differ in the clinical manifestation. Group B showed worst renal outcome. Gene frequencies of homozygous CFHR1 deletion were 73.3%, 2.7% and 1% in Group A, Group B+C and the control, respectively. In our cohort, we observed a relatively high incidence of anti-CFH-association. Clinical outcomes largely conformed to the previous reports. Although the size is limited, this cohort provides a reassessment of clinicogenetic features of aHUS in Korean children. This article is protected by copyright. All rights reserved.
    Pediatrics International 12/2014; DOI:10.1111/ped.12549 · 0.73 Impact Factor
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    ABSTRACT: Purposes To evaluate the mineral and bone disorders in children with chronic kidney disease (CKD) stage I to V predialysis. Methods Pediatric subcohort of KNOW-CKD (KoreaN cohort study for Outcome in patients With CKD) enrolled children (younger than 20 years) with CKD stage I-V (pre-dialysis) from five major pediatric nephrology centers in Korea and collected medical data associated with CKD-mineral and bone disorder. Results Total number of 300 patients (male:female=199:101) was included in this study. Serum phosphorus (mean ± standard deviation 4.89±0.75, 4.6±0.83, 4.63±0.85, 5.13±1.37, 5.35±1.2 from CKD stage I to V, p=0.0002), fibroblast growth factor (FGF)-23 (32.29±42.04, 41.33±41.00, 70.68±121.06, 67.9±66.95, 121.74±139.36, p=0.0030) and the prevalence of hyperphosphatemia (8.51%, 10.64%, 25.53%, 25.53%, 29.79%, p=0.010) increased as CKD progressed. Intact parathyroid hormone (iPTH) increased (40.84±40.37, 44.13±20.2, 78.93±65.21, 181.39±183.86, 313.85±324.95, p<0.001) and serum 1,25D3 level decreased (47.52±21.32, 37.43±12.26, 36.86±25.97, 28.29±15.81, 34.11±21.34, p<0.001) significantly as CKD aggravated. Serum iPTH (r=−0.608, p<0.0001) and FGF-23 (r=−0.4943, p<0.0001) showed negative correlation whereas 1,25D3 (r=0.3288, <0.0001) showed positive correlation with glomerular filtration rate. FGF-23 showed positive correlation with serum phosphorus (r=0.3342, p<0.0001), iPTH (r=0.3214, p<0.0001) and proteinuria (r=0.3609, p<0.0001), and negative correlation with urine phosphorus (r=−0.2597, p=0.0006). The prevalence of patients with increased alkaline phosphatase level increased significantly as CKD progressed (5.66%, 15.09%, 39.62%, 16.98%, 22.64%, p=0.042), which was due to increased prevalence of hyperparathyroidism (p<0.001). Active form vitamin D (0%, 3.77%, 11.88%, 40.74%, 68.89%, p<0.0001), calcium (2.13%, 0%, 9.90%, 4.44%, 62.22%, p<0.0001) and non-calcium phosphorous binders (0%, 0%, 0%, 0%, 13.33%, p<0.0001) were prescribed significantly more often in advanced CKD. Calcium x phosphorus was significantly increased in advanced CKD (11.59%, 17.39%, 28.26%, 21.01%, 21.74%, p=0.002). Conclusion As CKD progressed, hyperphosphatemia, hyperparathyroidism and 1,25D3 deficiency increased, serum FGF-23 level increased and urinary phosphorus excretion decreased in children with CKD stage I to V predialysis.
    06/2014; 33(2):A3–A4. DOI:10.1016/j.krcp.2014.05.021
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    ABSTRACT: Primary renal artery aneurysm has been estimated to account for an incidence of 0.015-1% with associated morbidities including renovascular hypertension and rupture. Renovascular hypertension associated renal artery aneurysms in children is not a common disease. In patients with complicated renal vascular disease, renal autotransplantation has been used as an alternative to percutaneous transluminal angioplasty, which may be hazardous in these situations. We report a case of a renal artery aneurysm in a 13-year-old Korean child presenting hypertension detected during school health examination. Preoperative workup demonstrated a 2.8×2.1×1.9 cm saccular aneurysm in the right renal hilum that was not amendable to endovascular repair. A surgical strategy including extracorporeal renal artery reconstruction with autotransplantation was applied in order to restore renal artery anatomy and to treat renovascular hypertension. Immediately he complained of severe right flank pain and postoperative doppler sonography revealed lack of perfusion. On the 5th day after autotransplantation, the patient underwent a transplant nephrectomy. He was well postoperatively and was found to have a normal kidney function and stable blood pressure control without antihypertensive medication. This is the first pediatric case of renal artery aneurysm in Korea who underwent extracorporeal repair followed by autotransplantation failure. More pediatric cases with renal artery aneurysm should be reported to identify therapeutic outcome and long term prognosis.
    Journal of the Korean Society of Pediatric Nephrology 01/2014; 18(1):51. DOI:10.3339/jkspn.2014.18.1.51
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    ABSTRACT: Although asymptomatic gross hematuria (GHU) is relatively common in children, its causes and clinical outcomes are not clearly defined. Children with asymptomatic GHU were examined and work-up was performed. Patients with recurrent GHU with proteinuria, or significant proteinuria, were considered for renal biopsy. The male:female ratio of all patients was 190:75, and the median age at onset of GHU was 6.4 years. Patients were grouped according to abnormalities on initial evaluation as follows: idiopathic (50%), proteinuria (21%), hypercalciuria (14%), sonographic abnormality (7%), hypocomplementemia (4%), familial (3%), and bleeding tendency (2%). Of patients with idiopathic GHU, 38% had a single episode, and of these, 34% had persistent microscopic hematuria, which resolved on follow-up., Late onset proteinuria was accompanied in 11% of patients with recurrent GHU. Nutcracker syndrome was diagnosed in one patient with recurrent idiopathic GHU. Of patients with recurrent GHU, 89% had no proteinuria on follow-up, and GHU and microscopic hematuria resolved in 97% and 89%, respectively. Our work-up protocol was useful for diagnosis and follow-up planning. Asymptomatic GHU in children was most commonly the idiopathic form. Overall, long-term prognosis appears to be benign; however, careful follow-up is essential.
    Nephrology 11/2013; 19(2). DOI:10.1111/nep.12181 · 1.86 Impact Factor
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    ABSTRACT: Pseudohypoaldosteronism (PHA) is a condition characterized by renal salt wasting, hyperkalemia, and metabolic acidosis due to renal tubular resistance to aldosterone. Systemic PHA1 is a more severe condition caused by defective transepithelial sodium transport due to mutations in the genes encoding the α (SCNN1A), β (SCNN1B), or γ (SCNN1G) subunits of the epithelial sodium channel at the collecting duct, and involves the sweat glands, salivary glands, colon, and lung. Although systemic PHA1 is a rare disease, we believe that genetic studies should be performed in patients with normal renal function but with high plasma renin and aldosterone levels, without a history of potassium-sparing diuretic use or obstructive uropathy. In the present report, we describe a case of autosomal recessive PHA1 that was genetically diagnosed in a newborn after severe hyperkalemia was noted.
    Journal of the Korean Society of Pediatric Nephrology 01/2013; 17(2):137. DOI:10.3339/jkspn.2013.17.2.137
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    ABSTRACT: Cystinuria is an autosomal recessive disease characterized by impaired transport of cystine and dibasic amino acids in the proximal renal tubule, resulting in the formation of cystine stones. It is believed to account for about 1% of all kidney stones and up to 10% of pediatric stones. Here we report a case of cystinuria with multiple renal stones confirmed by genetic mutational analysis. An 8-month-old girl was admitted to AMC with persistent fever and multiple renal stones. A renal sonogram showed multiple stones at the right renal pelvis, right distal ureter, and left renal medullary portion. An approximately 1 cm renal stone was extracted spontaneously, and stone analysis revealed it to be composed entirely of cystine. Cystinuria was confirmed by increased urine dibasic amino acid levels, including cysteine, and genetic mutational analysis showed the patient to be a homozygote for the pathogenic c. 1820del (p.L607fs) of SLC3A1. Despite treatment with oral hydration and urinary alkalinization, and restricted intake of animal protein, the stones increased in size and number. The patient has since been treated with tiopronin.
    Journal of the Korean Society of Pediatric Nephrology 01/2013; 17(2):122. DOI:10.3339/jkspn.2013.17.2.122
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    ABSTRACT: BACKGROUND: Health-related quality of life (HRQOL) is an essential subject for children with end-stage renal disease (ESRD) and their families. METHODS: We performed a cross-sectional investigation of HRQOL in children undergoing renal replacement therapies, such as dialysis and renal transplantation, using the 34-item Pediatric Quality of Life Inventory 3.0 End-Stage Renal Disease (PedsQL 3.0 ESRD) module. We assessed 92 ESRD patients aged 2-18 from four Korean university hospitals. RESULTS: The male:female ratio was 44:48, and the most common cause of ESRD was chronic glomerulonephritis. Fifty-five children were treated by dialysis, and 37 received renal transplantation. Transplant patients had better HRQOL than dialysis patients in two domains in parent proxy reports: "About my kidney disease" and "Worry." In child self-reports, transplant patients had better HRQOL than dialysis patients in one domain: Treatment problems. However, there were no significant differences in total QOL scores between peritoneal dialysis (PD) and transplant patients in child self-reports. In addition, there were differences in the ESRD module scores between child self- and parent proxy reports. Children usually reported better QOL than their parents. Child self-reports showed significantly higher QOL scores than parent proxy reports in the domains of General fatigue, Family & peer interaction, and Worry. Children on PD self-reported a significantly higher QOL than children on hemodialysis (HD). CONCLUSIONS: The PedsQL 3.0 ESRD module may be useful as an ESRD-specific instrument to evaluate HRQOL in children; however, a larger, longitudinal prospective study is warranted.
    Pediatric Nephrology 07/2012; 27(12). DOI:10.1007/s00467-012-2262-1 · 2.88 Impact Factor
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    ABSTRACT: Health-related quality of life is a very important issue in children with end-stage renal disease and their family. Moreover, this can be a lifelong problem. In this study, we performed a cross-sectional investigation of the health-related quality of life in Korean children, undergoing renal replacement therapies, such as dialysis and renal transplantation. We validated the Korean version of the PedsQL 3.0 End-Stage Renal Disease Module by comparing with the PedsQL 4.0 Generic Core Scales. A total of 92 pediatric patients with end-stage renal disease, aged 2-18 year old, were enrolled in four teaching hospitals in Korea. The module was acceptable for both parent proxy-report and child self-report. The response rate was acceptable, since no reminders were delivered. A large proportion of the responders answered > 90% of the items, which suggests a good face validity. The PedsQL 4.0 Generic Core Scales and the PedsQL 3.0 End-Stage Renal Disease Module showed minimal missing values in the current study, which supported feasibility. The validation analyses revealed acceptable floor and ceiling effects and an acceptable construct validity. The PedsQL 3.0 End-stage Renal Disease Module may be useful as an end-stage renal disease -specific instrument in the evaluation of the health-related quality of life in Korean children; however, a larger, longitudinal prospective study is needed.
    Health and Quality of Life Outcomes 06/2012; 10:59. DOI:10.1186/1477-7525-10-59 · 2.10 Impact Factor
  • Yoon Jung Lee, Joo Hoon Lee, Young Seo Park
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    ABSTRACT: We prospectively determined the risk factors for renal scar formation after the first episode of acute pyelonephritis as confirmed on dimercapto-succinic acid scintigraphy in children younger than 1 year. A total of 213 infants with acute pyelonephritis were enrolled in the study. Infants with urological abnormalities other than vesicoureteral reflux were excluded from analysis. Followup scanning was performed 6 months after acute pyelonephritis and voiding cystourethrography was performed after the acute phase of infection. Possible risk factors were evaluated including gender, peak fever, duration of fever before and after treatment with antibiotics, white blood cell count, C-reactive protein concentration, presence of vesicoureteral reflux and reflux grade. Six months after acute pyelonephritis 37 of 213 (17.4%) infants and 41 of 248 (16.5%) renal units with acute photon defects on initial dimercapto-succinic acid scintigraphy had renal scars. The rates of scar formation were significantly higher in infants with vesicoureteral reflux than in those without (39.4% vs 7.5%, p <0.001, OR 9.433) and in renal units with vesicoureteral reflux than in those without (39.4% vs 8.2%, p <0.001, OR 7.237). Renal scar formation was related to reflux grade (none-8.2%, grade I-20%, grade II-22.7%, grade III-40%, grade IV-70%, grade V-55.6%, p <0.001) but not to any other clinical or laboratory variables. The presence of vesicoureteral reflux was the only independent risk factor for renal scar formation after acute pyelonephritis in infants. The prevalence of renal scarring was significantly correlated with reflux grade. Voiding cystourethrography is necessary in infants after the first acute pyelonephritis episode is confirmed on dimercapto-succinic acid renal scintigraphy.
    The Journal of urology 03/2012; 187(3):1032-6. DOI:10.1016/j.juro.2011.10.164 · 3.75 Impact Factor
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    ABSTRACT: The aim of our study was to investigate the characteristics of the peritoneal dialysis (PD) - related peritonitis and to evaluate the effectiveness of the empirical antibiotics recommended by the International Society for Peritoneal Dialysis in Korean children.
    Journal of the Korean Society of Pediatric Nephrology 01/2012; 16(2):80. DOI:10.3339/jkspn.2012.16.2.80
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    ABSTRACT: We report a patient with immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome with a novel splicing mutation of the FOXP3 gene. The patient is a boy, born at 39 + 2 weeks gestation with a birth weight of 3,280 g. The family history was unremarkable. He was well until 11 months of age, when he was diagnosed with type 1 diabetes mellitus. The level of urine C-peptide was 0.58 μg/day (normal range, 44-116 μg/day). Glutamic acid decarboxylase autoantibody was not detected, but a high level of anti-insulin antibody (50 IU/mL; normal range, <5 IU/mL) was noted. This patient presented with unusual clinical features, including pure red cell aplasia, membranous glomerulopathy, and posterior reversible encephalopathy syndrome after a vaccination against influenza A H1N1 virus. The diagnosis of IPEX was made when the patient was 11 years old, which is quite late compared with typical cases. Conclusion: Although IPEX syndrome is usually a disease of infancy, it should not be ruled out solely on the basis of age. IPEX presentation is so variable that it should be suspected in a male child with one or more autoimmune disorders and severe infections.
    European Journal of Pediatrics 12/2011; 170(12):1611-5. DOI:10.1007/s00431-011-1588-1 · 1.98 Impact Factor
  • American Journal of Kidney Diseases 12/2011; 58(6):1042-3. DOI:10.1053/j.ajkd.2011.09.007 · 5.76 Impact Factor
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    ABSTRACT: Bartter syndrome (BS) is clinically classified into antenatal or neonatal BS (aBS) and classic BS (cBS) as well as five subtypes based on the underlying mutant gene; SLC12A1 (BS I), KCNJ1 (BS II), CLCNKB (BS III), BSND (BS IV) and CASR (BS V). Clinico-genetic features of a nationwide cohort of 26 Korean children with BS were investigated. The clinical diagnosis was aBS in 8 (30.8%), cBS in 15 (57.7%) and mixed Bartter-Gitelman phenotype in 3 cases (11.5%). Five of eight patients with aBS and all 18 patients with either cBS or mixed Bartter-Gitelman phenotype had CLCNKB mutations. Among the 23 patients (46 alleles) with CLCNKB mutations, p.W610X and large deletions were detected in 25 (54.3%) and 10 (21.7%) alleles, respectively. There was no genotype-phenotype correlation in patients with CLCNKB mutations. Twenty-three (88.5%) of the 26 BS patients involved in this study had CLCNKB mutations. The p.W610X mutation and large deletion were two common types of mutations in CLCNKB. The clinical manifestations of BS III were heterogeneous without a genotype-phenotype correlation, typically manifesting cBS phenotype but also aBS or mixed Bartter-Gitelman phenotypes. The molecular diagnostic steps for patients with BS in our population should be designed taking these peculiar genotype distributions into consideration, and a new more clinically relevant classification including BS and Gitelman syndrome is required.
    Nephrology Dialysis Transplantation 08/2011; 27(4):1516-21. DOI:10.1093/ndt/gfr475 · 3.49 Impact Factor
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    ABSTRACT: MYH9-related disorders are a group of autosomal, dominantly inherited disorders caused by mutations of the MYH9 gene, which encodes the non-muscle myosin heavy chain IIA (NMMHC-IIA). May-Hegglin anomaly and Sebastian, Fechtner, and Epstein syndromes belong to this group. Macrothrombocytopenia is a common characteristic associated with MYH9-related disorders, and basophilic cytoplasmic inclusion bodies in leukocytes (Döhle-like bodies), deafness, cataracts, and glomerulopathy are also found in some patients. In this study, renal manifestations of 7 unrelated Korean patients with MYH9-related disorders were analyzed. Of a total of 7 patients, 4 had disease-related family histories. One familial case had a mutation in the tail domain of NMMHC-IIA and showed milder renal involvement with preserved renal function by his 30s. Among the 3 familial cases without renal involvement, 2 had mutations in the tail domain of NMMHC-IIA and 1 had a mutation in the motor domain. The remaining 3 sporadic cases had severe renal involvement with rapid progression to end-stage renal disease and mutations located in the motor domain. In summary, mutations in the motor domain of NMMHC-IIA and negative family history were associated with severe renal involvement in patients with MYH9-related disorders. These results are in agreement with those of previous reports.
    Pediatric Nephrology 04/2011; 26(4):549-55. DOI:10.1007/s00467-010-1735-3 · 2.88 Impact Factor
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    Joo Hoon Lee
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    ABSTRACT: The treatment of pediatric patients with chronic renal disease comprises management of nutritional imbalance, fluid, electrolyte, and acid-base disturbances, mineral bone disease, anemia, hypertension, and growth retardation. The treatment also includes administration of appropriate renal replacement therapy, if required. Adequate dietary intake of carbohydrates, fats, and proteins and caloric intake must be encouraged in such patients to ensure proper growth and development. In addition, fluid, electrolyte, and acid-base status must be regularly monitored and should be well maintained. Serum calcium, phosphorus, and parathyroid hormone levels must be maintained at their target range, which are determined on the basis of the glomerular filtration rate, to avoid the development of mineral bone disease. This can be achieved by using phosphorus binders and vitamin D analogues. An erythropoiesis-stimulating agent must be administered along with iron supplementation to maintain the hemoglobin level of the patients between 11-12 g/dL. Hypertension must be controlled with adequate water and sodium balance and appropriate antihypertensive agents. Administration of recombinant human growth hormone is recommended to improve the final adult heights.
    Korean Journal of Pediatrics 01/2009; 52(10). DOI:10.3345/kjp.2009.52.10.1061
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    ABSTRACT: This study was performed to report the diagnosis and treatment of nephrotic syndrome manifesting in the first year of life.
    Journal of the Korean Society of Pediatric Nephrology 01/2009; 13(2). DOI:10.3339/jkspn.2009.13.2.161
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    ABSTRACT: This study assessed the incidence and outcome of congenital anomalies of the kidney and urinary tract (CAKUT) detected by prenatal ultrasonography
    Korean Journal of Pediatrics 01/2009; 52(4). DOI:10.3345/kjp.2009.52.4.464
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    ABSTRACT: Peritoneal dialysis (PD) is the major form of dialysis in use for infants and children with end-stage renal disease (ESRD). The aim of this study was to gain insight into the current status of children on PD in Korea.
    Journal of the Korean Society of Pediatric Nephrology 01/2009; 13(2). DOI:10.3339/jkspn.2009.13.2.176
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    ABSTRACT: Mutations in the SLC22A12 gene, which encodes a uric acid transporter, URAT1, are associated with renal hypouricaemia. This study was designed to measure serum uric acid (Sua) levels and allele frequencies of two common mutations in SLC22A12, W258X and R90H, in healthy Korean subjects. A total of 909 unrelated Korean adults (male : female, 1:1.23; mean age, 48.4 +/- 11.0 years) were recruited among those who had taken a routine health check-up in a health centre in 2003. None of them had hypertension, diabetes mellitus, kidney diseases or liver diseases. Genotyping for W258X and R90H was performed using the TaqMan method. The prevalences of hyperuricaemia (Sua levels, >416 micromol/L) and hypouricaemia (Sua levels, <178 micromol/L) were 4.6% and 3.3%, respectively. A marked male preponderance in the hyperuricaemic group was noted, and the men revealed higher Sua than the women. The Sua showed a positive correlation with serum creatinine level and blood pressure. In the hypouricaemic group, the allele frequencies of W258X and R90H were 11.7% and 6.7%, respectively, and the proportion of subjects with one or both of the mutant alleles was 33.3%. Hyperuricaemic subjects never had either mutation. The W258X and/or R90H mutations in the SLC22A12 gene are one of the major factors responsible for hypouricaemia, and one-third of the hypouricaemic subjects had one or both of the mutant alleles.
    Nephrology 11/2008; 13(8):661-6. DOI:10.1111/j.1440-1797.2008.01029.x · 1.86 Impact Factor

Publication Stats

230 Citations
53.73 Total Impact Points

Institutions

  • 2008–2014
    • University of Ulsan
      • • Department of Pediatrics
      • • College of Medicine
      Urusan, Ulsan, South Korea
    • Duksung Women's University
      • Department of Pharmacy
      Sŏul, Seoul, South Korea
  • 2006–2014
    • Asan Medical Center
      • Department of Pediatrics
      Sŏul, Seoul, South Korea
  • 2011
    • Seoul National University Hospital
      Sŏul, Seoul, South Korea
  • 2005–2009
    • Ulsan University Hospital
      Urusan, Ulsan, South Korea
  • 2001
    • Seoul National University
      • Department of Pediatrics
      Sŏul, Seoul, South Korea