Association between polymorphisms in Interleukin-17 receptor A gene and childhood IgA nephropathy / 소아과

PURPOSE: Interleukin-17 (IL-17) is produced by activated CD4+T cells and exhibits pleiotropic biological activity on various cell types. IL-17 was reported to be involved in the immunoregulatory response in IgA nephropathy (IgAN). Our aim was to investigate the association between single-nucleotide polymorphisms (SNPs) in IL-17 receptor A (IL-17RA) gene and childhood IgAN. METHODS: We analyzed the SNPs in the IL-17RA in 156 children with biopsy-proven IgAN and 245 healthy controls. We divided the IgAN patients into 2 groups and compared them with respect to proteinuria (4 mg/m2/h, 40 mg/m2/h, respectively) and the presence of pathological levels of biomarkers of diseases such as interstitial fibrosis, tubular atrophy, or global sclerosis. RESULTS: No difference was observed between the SNP genotypes rs2895332, rs1468488, and rs4819553 between IgAN patients and control subjects. In addition, no significant difference was observed between allele frequency of SNPs rs2895 332, rs1468488, and rs4819553 between patients in the early and advanced stage of the disease. However, significant difference was observed between the genotype of SNP rs2895332 between patients with proteinuria (>4 mg/m2/h) and those without proteinuria (codominant model OR 0.36, 95% CI 0.19-0.66, P<0.001; dominant model OR 0.35, 95% CI 0.17-0.69 P=0.002; recessive model OR 0.12, 95% CI 0.01-1.06 P=0.025). CONCLUSION: Our results indicate that the SNP in IL-17RA (rs2895332) may be related to the development of proteinuria in IgAN patients.

Association of HLA-G gene promoter haplotype with childhood IgA nephropathy in the Korean population / 소아과

PURPOSE: IgA nephropathy (IgAN) is the most commonly occurring form of chronic glomerulonephritis in pediatric cases. Human leukocyte antigen (HLA) genes have been implicated in various inflammatory and autoimmune diseases. The present study was conducted to investigate the association between 2 single nucleotide polymorphisms (SNPs) of the HLA-G gene and childhood IgAN. METHODS: The authors analyzed and compared HLA-G gene SNPs (rs1736936 and rs2735022) in 174 patients with childhood IgAN and in 438 healthy controls. In addition, IgAN patients were dichotomized and compared with respect to proteinuria (4 mg/m2/hour), the presence or absence of podocyte foot process effacement, and the presence of pathologically early and advanced disease markers such as interstitial fibrosis, tubular atrophy, or global sclerosis. RESULTS: No significant SNP frequency differences were observed for the HLA-G gene between IgAN patients and the control group. Moreover, no significantly associated SNP was observed with the presence of proteinuria, podocyte foot process effacement, or pathologically advanced markers. However, the haplotype, composed of rs1736936 and rs2735022, showed a significant association with the susceptibility to develop childhood IgAN (haplotype T/C: dominant model, P=0.049; haplotype C/T: recessive model, P=0.030). CONCLUSION: Our results indicate that rs1736936 and rs2735022 as the HLA-G gene promoter haplotype might be associated with the susceptibility to develop childhood IgAN in the Korean population.

Two Korean Infants with Genetically Confirmed Congenital Nephrotic Syndrome of Finnish Type

Congenital nephrotic syndrome is defined as nephrotic syndrome which manifests in utero or during the first 3 months of life. The prototype of congenital nephrotic syndrome is congenital nephrotic syndrome of Finnish type (CNF, OMIM #602716), which is caused by loss-of-function mutations of the nephrin gene (NPHS1). There have been few clinical case reports of CNF in Korea, but none of which was confirmed by genetic study. Here, we report two children with congenital nephrotic syndrome. Genetic analysis of the NPHS1 gene revealed compound heterozygous frame-shifting mutations (c.2156_2163 delTGCACTGC causing p.L719DfsX4 and c.3250_3251insG causing p.V1084GfsX12) in one patient and a missense mutation (c.1381G>A causing p.R460Q) and a nonsense mutation (c.2442C>G causing p.Y814X) in the other patient. The nonsense mutation was novel. The clinical courses of the patients were typical of CNF. This is the first report of genetically confirmed CNF in Korea to date. The early genetic diagnosis of CNF is important for proper clinical management of the patients and precise genetic counseling of the families.

Research Related to Chronic Kidney Disease in BMI >25 Overweight Children

PURPOSE: Chronic kidney disease (CKD) and obesity are the worldwide public health problem. Obesity is an already well-established risk factor for CKD. The objective of this study is to evaluate the relationship between high BMI and increased risk for nephropathy by clinical data. METHODS: Study group were 26 patients who had BMI> or =25 kg/m2 and control group were 49 patients with BMI<25 kg/m2. Both groups received renal biopsy in Kyung Hee Medical Center between 2003. Jan.-2007. Dec. BMI was calculated from measured weight and height when they were admitted to the hospital. We collected laboratory data such as CBC and blood chemistry. RESULTS: Our hypothesis was that overweight and obesity are associated with incidence and progression of CKD. From kidney biopsy, we found IgAN 17, MesPGN 5, HSPN 2, Intestitial nephritis 1, IgMN 1 (total 26) in the study group whereas IgAN 22, MesPGN 17, HSPN 3, MGN 3, benign hematuria 2, MPGN 1, Intestitial nephritis 1, (total 49) were found in the control group. There was no significant difference between the two groups. Overweight patients demonstrated significantly higher platelet, TG, ALT, and uric acid level compared to control group. CONCLUSION: We identified a significant relationship between overweight and development of CKD. These results suggest that overweight children have an increased risk for CKD than those who are not obese. So, we should pay attention to children with overweight who have CKD and earlier weight management is crucial to prevent aggravation of CKD.

The Comparison between FSGS and MCNS Using Proteomic Method in Childhood Nephrotic Syndrome; Preliminary Study

PURPOSE: FSGS do not respond well to any kind of therapy and gradually progress to end-stage renal disease. This study was conducted to investigate the difference of protein expression between MCNS and FSGS as a preliminary study for understanding the pathophysiology of FSGS. METHODS: Renal biopsy samples of MCNS and FSGS were obtained, which was diagnosed by one pathologist. They were solubilized with a conventional extraction buffer for protein extraction. The solution was applied on immobilized linear gradient strip gel (pH 4-7) using IPGphor system. Silver staining was carried out according to standard method. Protein identification was done by searching NCBI database using MASCOT Peptide Mass Fingerprint software. RESULTS: The differences in protein expressions between MCNS and FSGS were shown by increased or decreased protein spots. Most prominently expressed spot among several spots in FSGS was isolated and analyzed, one of which was glutathione S-transferase (GST) P1-1, whereas it was not found in MCNS. So GSTP1-1 was considered as the one of the key biomarkers in pathogenesis of FSGS. CONCLUSION: This result would be helpful in diagnosing FSGS and researching FSGS. Further studies for glutathione S-transferase P1-1 might be necessary to elucidate the mechanisms regarding FSGS.

A Case of Urachal Cyst Infection Occurring During Corticosteroids Therapy in a Patient with IgA Nephropathy

The urachus is a normal embryonic remnant of the primitive dome. It generally exists as a fibrous cord extending from the dome of the bladder to the umbilicus. Disorders of the urachus are developed as a result of its incomplete regression. The urachal cyst is the most common urachal anomaly, and is usually asymptomatic in infancy and childhood. However, when the cysts are large or accompanied with secondary infection, they may be detected in its early stage. A sonography or CT scan may be helpful to confirm the diagnosis of urachal cyst. The managements of infected urachal cyst are varied from simple drainage to radical excision. Here, we report an unusual case of urachal cyst infection that occurred during corticosteroids therapy in a girl with IgA nephropathy.

Current status of pediatric kidney transplantation / 소아과

Renal transplantation is the treatment of choice for children with end-stage renal disease. The outcome of pediatric kidney transplantation has improved dramatically in recent years, with lower acute rejection rates, superior graft survival, and low mortality. These improvements have allowed increased attention to other aspects of care for long-term survivors. Taking this into consideration, this review article will focus on the key issues related to pediatric kidney transplantation such as growth, neurocognitive function, nonadherence, and posttransplantation infectious complications, including lymphoproliferative disease, to broaden the understanding of pediatricians who provide pre-and postoperative care to children with end-stage renal disease.

The enabled homolog gene polymorphisms are associated with susceptibility and progression of childhood IgA nephropathy

The enabled homolog gene (ENAH, hMena) is abundantly expressed in mesangial tissue, and might play an important role in inflammatory processes of IgA nephropathy (IgAN). The present study was conducted to investigate the association between single nucleotide polymorphisms (SNPs) of the ENAH and childhood IgAN. We analyzed 12 SNPs of ENAH in 176 patients with childhood IgAN and 397 healthy controls. In addition, IgAN patients were dichotomized and compared with respect to several clinical and pathological parameters. Genotyping data showed significant differences between IgAN patients and controls in the frequency of rs2039620, rs12034829, and rs3795443. On comparison of patients with proteinuria to those without proteinuria ( 4 mg/m2/h), rs12043633 was significantly different between the two groups. With regard to maximum proteinuria ( 4 mg/m2/h), rs3795443, rs4653643, rs6751, rs10799319, rs7555139, rs576861, and rs487591 showed significant allele frequency differences. For patients with and without gross hematuria, rs4653643, rs6751, rs10799319, rs7555139, rs576861, and rs487591 showed significant allele frequency differences. The rs3795443 was found to be associated with progression of pathological findings. Our results suggest that ENAH polymorphisms are associated with increased susceptibility, development of proteinuria and gross hematuria, and pathological progression of childhood IgAN.

A Case of Vancomycin-Resistant Enterococci P eritonitis in a Pediatric P atient on CAPD Successfully Treated with Linezolid

Peritonitis is one of the major complications of CAPD(continuous ambulatory peritoneal dialysis). Recently, multidrug-resistant organisms, such as vancomycin-resistant enterococcus (VRE) have been rarely reported by the pathogen as of CAPD-associated peritonitis. But, there is limited information on choices of effective therapy for VRE peritonitis in patients undergoing CAPD. We present a pediatric case of successful treatment of CAPD-associated peritonitis due to VRE with linezolid, and review of the literature.

A Case of Diabetic Nephropathy in a Child with Type 1 Diabetes

Diabetes mellitus(DM) is a metabolic syndrome caused by deficiency of insulin secretion and a consequence of insulin resistance. Poor glycemic control is a common finding in children with Type 1 DM(T1DM). Approximately 60% of the young patients with T1DM develop abnormalities in the eyes and 15-20% in the kidney. Diabetic nephropathy (DN) is a serious metabolic complication of T1DM that leads to renal failure. Some clinical studies report that the duration of prepubertal diabetes may contribute less to the development of microvascular complications than pubertal and postpubertal duration. There have been few cases of DN in prepubertal patients with T1DM in Korea. Thus we report a case of a 12-year-old female with T1DM who had poor glycemic control and was diagnosed as DN in a prepubertal period. It was proven by renal biopsy after microscopic hematuria and proteinuria were detected through the mass school urinary screening program.

Two Cases of Rhabdomyolysis after E xcessive E xercise

Rhabdomyolysis is a syndrome involving the breakdown of skeletal muscle causing myoglobin and other intracellular proteins and electrolytes to leak into the circulation. There are various causes of acute rhabdomyolysis in childhood, such as direct trauma to muscle, muscle necrosis from ischemia, inflammation in muscle, or exposure to drugs and toxins. The most-important complication of this disorder is acute renal failure (ARF). However, the contributing factors to the development of ARF in children with rhabdomyolysis remain obscure. We report two cases of rhabdomyolysis after excessive exercise.

The impact of early detection through school urinary screening tests of membranoproliferative glomerulonephritis type / 소아과

PURPOSE: Since 1998, school urinary screening tests have been performed on Korean school children. We could detect and treat so many asymptomatic chronic renal disease in early stage. We investigated the efficacy of school urinary screening tests from children with membranoproliferative glomerulonephritis (MPGN) type I. METHODS: We analyzed the characteristics and prognosis of 18 patients with MPGN type I who admitted after 1996 and received steroid therapy with or without cyclosporine. These patients were divided into two groups. Group A (asymptomatic patients detected by school urinary screening tests) consisted of 7 patients; Group S (symptomatic patients) consisted 11 patients. RESULTS: Mean follow-up duration was 6.3 years (from 2 to 11 years). Urinary protein excretion was 1.1 g/day in group A and 6.6 g/day in group S. 24 hour creatinine clearance (mL/min/1.73m2) was 134.3 in group A and 82.3 in group S. No patients in group A had renal insufficiency, but three patients in group S had renal insufficiency and one patient required peritoneal dialysis. CONCLUSION: Early detection by school urinary screening tests improves prognosis of MPGN type I.

Long-term Follow up of Congenital Adrenal Hyperplasia Patients with Hyponatremia

Congenital adrenal hyperplasia (CAH) caused by 21-hydroxylase deficiency is an autosomal recessive disease, which leads to cortisol and aldosterone deficiency and hyperandrogenism. Typical medical treatment includes oral glucocorticoid and mineralocorticoid administration to suppress adrenal androgens and to compensate for adrenal steroid deficiencies. Usually, they have been managed with hydrocortisone (cortisone) and fludrocortisone (florinef). However, some patients stopped taking medicine without the doctor's consent. Among these patients, four cases of CAH patients showing the presence of hyponatremia as an initial electrolyte disorder were found with adrenal adenoma discovered by abdominal computerized tomography scan. Hypersecretion of adrenocorticotrophic hormone may play a role in the development of adrenal tumor and chronic poor compliance to therapy appears to be associated with development of the tumor. Two cases were managed with adrenalectomy because of increasing adrenal tumor size and virilization. Whereas the other two cases did not increase in size and were observed without adrenalectomy. Therefore, it is important that patients with CAH maintain steroid medication to avoid the appearance of adrenal tumor.

The Correlation between the Severity of Hypoxic Ischemic Encephalopathy and the Development of Acute Renal Failure in Asphyxiated Neonates

PURPOSE: We performed this study to determine the incidence of acute renal failure(ARF) in birth asphyxia and to correlate the severity of asphyxia and hypoxic-ischemic encephalopathy (HIE) and ARF in asphyxiated neonates. METHODS: Data was retrospectively collected from the medical records of 33 patients with neonatal asphyxia and of 33 neonates with no asphyxia. On the basis the 5-minute Apgar score, the asphyxiated neonates were further grouped into mild(6 or 7), moderate(4 or 5), and severe asphyxia(3 or less). Asphyxiated neonates with HIE were staged by the Sarnat and Sarnat scoring system. We compared serum creatinine, blood urea nitrogen, electrolytes, and urine output on day 3 of life and the incidence and severity of intraventricular hemorrhage(IVH) between each group. RESULTS: ARF occurred in 8(24.2%) asphyxiated neonates. Of these, 3(37.5%) were oliguric, while 1(10.0%) patient with mild asphyxia, 2(18.2%) of moderate asphyxia, and 5(41.7%) with of severe asphyxia had ARF(P>0.05). One(25%) patient with stage I HIE, 4(50%) with stage II HIE, and 3(75%) of HIE with stage III HIE developed ARF(P<0.01). There was no statistical correlation between the severity of asphyxia and HIE stage. One(7.7%) patient with grade 1 IVE, 0(0.0%) with grade 2 IVH, 2(66.7%) with grade 3 IVH, and 2(100.0%) with grade 4 IVH had ARF(P<0.01). Mortality was higher in asphyxiated neonates with ARF(P<0.05). There was no significant difference between the oliguric and non-oliguric renal failure. CONCLUSION: We found that the greater the degree of HIE, the higher was the incidence of ARF. Asphyxiated neonates with ARF had a poorer prognosis.

The Effect of Recombinant Human Growth Hormone on Growth in Children with Nephropathy Receiving Long-term Steroid Therapy

PURPOSE: Growth retardation is one of the serious problems in children with nephropathy requiring long-term steroid therapy. We observed the efficacy and safety of recombinant human growth hormone(rhGH) on the growth in children with long-term steroid therapy. METHODS: We studied 60 children(male 47, female 13) with nephropathy who received rhGH (1 U/kg/week) for more than 0.5 years(1.39+/-1.12). Their mean age was 11.0 years (11.17+/-2.62). They received steroid therapy from January 1987 through July 2005, and the mean duration of steroid therapy was 4.32+/-2.97 years. Among the patients, there were 32 nephrotic syndrome, 9 IgA nephropathy, 4 mesangial proliferative glomerulonephritis, 4 focal segmental glomerulosclerosis, 2 Henoch Schonlein nephritis, 2 Alport syndrome and 7 other cases. Data were gathered on the growth parameters, such as growth velocity, height standard deviation score(SDS), IGF-1, IGFBP-3, bone mass density(BMD) and general chemistry changes. RESULTS: Height velocity increased significantly with rhGH therapy from 3.29+/-1.95 to 8.66+/-3.75(cm/yr) and height SDS decreased from -0.72+/-0.93 to -1.04+/-0.86 at one year after steroid therapy but increased to -0.55+/-0.96 at one year after rhGH administration(P<0.05). BMD improved from 0.71+/-0.14 to 0.79+/-0.15 g/cm2(P<0.05). IGF-1 increased from 445.09+/-138.01 to 506.62+/-181.31 ng/mL(P<0.05). IGFBP-3 decreased from 4073.75+/-700.78 to 3933.61+/-789.25 ug/L numerically, but there was no statistically significant difference(P=0.533). CONCLUSION: The administration of rhGH in the short stature patients who received long- term steroid therapy showed improvement in growth parameters such as SDS, growth velocity, and BMD without significant side-effects or changes in the biochemical parameters.

The Differences in Frequencies and Clinical Manifestations According to the Causes of Membranous Nephropathy in Children

PURPOSE: To report the decreasing incidence of HBV(Hepatitis B virus)-associated membranous nephropathy in children after HBV vaccination and to elucidate the clinical course and treatment strategies of IMN (Idiopathic membranous nephropathy). METHODS: We retrospectively reviewed the clinico-pathological findings of HBV-MN and IMN patients who underwent a renal biopsy from 1986 to 2005. We compared the HBV-MN and the IMN groups and the remission and the non-remission groups of patients with IMN. RESULTS: Among 24 cases of MN patients, HBV-MN comprised 6 cases(25%) and IMN 18 cases(75%). Clinical masnifestations were nephrotic syndrome(3 cases, 50%), nephritic syndrome(1 case, 16.7%), asymptomatic(2 cases, 33.4%) in the HBV-MN group, asymptomatic(10 cases, 55.5%), nephrotic syndrome(5 cases, 27.8%), and gross hematuria(3 cases, 16.7%) in the IMN group. From 1996 to 2000, there were 2 cases(28%) of HBV-MN and 5 cases(72%) of IMN. After 2001, all 10 cases were IMN. In the HBV-MN group, 4 cases(66.7%) received interferon and 1 case received methylprednisolone pulse therapy. In the IMN group, 16 cases (88.9%) received methylprednisolone, 8 cases(44.4%) were in complete remission, 2 cases (11.1%) were in partial remission, 2 cases(11.1%) were in chronic renal failure, and 5 cases (27.8%) were lost to follow-up with sustained proteinuria, 1 case(5.6%) continued to have frequent relapse of nephrotic syndrome without renal insufficiency. In the comparison between remission and non-remission groups, nephrotic range proteinuria and hypertension were more significantly common in the non-remission group(P<0.05). CONCLUSION: With HBV vaccination, HBV-MN has decreased markedly. IMN is a rare glomerular disease in children. Because the prognosis for patients with nephrotic range proteinuria is poor, this group needs more aggressive treatment.

Analysis of 1559 Kidney Biopsies: A Single Center Study

PURPOSE: To analyse the results of the renal biopsies and the clinical diagnoses of patients who had undergone percutaneous kidney biopsies in the department of pediatrics at Kyunghee University Hospital for 22 years from 1984 to 2005. METHODS: We retrospectively reviewed the medical records of 1559 patients and analyzed the chief complaints that led to a renal biopsy, age, sex, histopathologic findings and diagnosis. Routine kidney biopsies were performed by automated gun biopsy guided by real time ultrasonography. The diagnoses were made based on the specimen's light microscopy, immunofluorescence microscopy and electron microscopy findings and clinical symptoms and signs. RESULTS: The mean age of the patients was 10 years with the male to female ratio being 1.3:1. The chief complaints that led to a renal biopsy included hematuria only(753 cases, 48.3%), proteinuria only(125 cases, 8.0%) and hematuria combined with proteinuria(537 cases, 34.4%). The most frequent histopathological finding was primary glomerular disease(75.4%) which included IgA nephropathy(30.1%) and mesangial proliferative glomerulonephritis(27.6 %). Systemic disease comprised 11.4% which included Henoch-Shonlein nephritis(10.5%) and lupus nephritis(0.8%). Alport syndrome was found in 1.1% of cases which was attributed to hereditary causes. 628 children(40.3%) visited the clinic due to abnormal school urine screening abnormalities and among these, 237 children had mesangial proliferative glomerulonephritis and 234 children who had IgA nephropathy were managed thereafter. CONCLUSION: IgA nephropathy and mesangial proliferative glomerulonephritis were the two major forms of primary glomerulonephritis found in Korean children who had kidney biopsies from 1984 to 2005.

Urinary Transforming Growth Factor-beta-inducible Gene-h3 in Patients with Glomerular Diseases / 대한신장학회잡지

BACKGOUND: Transforming growth factor-beta (TGF-alpha) has been implicated in the pathogenesis of a number of kidney diseases. However, TGF-alpha is secreted in a latent form requiring extracellular modification to become biologically active. Recently, the activity of TGF-alpha has been assessed by the measurement betaig-h3, a novel TGF-alpha induced gene product. Thus we evaluated the pattern of urinary betaig-h3 expression in various glomerular diseases. METHODS: 64 patients with biopsy-proven primary glomerulonephritis (FSGS 6, HSPN 16, IgAN 20, MPGN I 7, and MesPGN 15), 10 patients with nephrotic syndrome and 12 healthy controls were enrolled in the study. A total 86 subjects (51 males, 59.3% and 35 females, 40.7%, mean age 13.9+/-4.28 years) constituted study population. First morning urine were collected and betaig-h3 in the urine was determined by indirect competitive ELISA (Regen Biotech Inc, Seoul, Korea). RESULTS: betaig-h3 excretion was significantly higher in the urine from patients with HSPN (27.5+/-6.46, p=0.002), with IgAN (40.83+/-12.27, p=0.026), with MPGN I (21.64+/-7.29, p=0.042), MesPGN (26.42+/-6.68, p=0.007). In patients with FSGS (21.65+/-17.12) and minimal change nephrotic syndrome (6.26+/-2.18), mean urinary betaig-h3 excretion was not significant higher than that in control group (3.56+/-0.78). CONCLUSION: Urinary betaig-h3 excretion was high in proliferative renal diseases. However, betaig-h3 excretion was not high in non-proliferative renal diseases.

Histopathologic Diagnosis and Outcome of Renal Biopsied Pediatric Nephrotic Syndrome

PURPOSE: To determine the histological findings and treatment outcome in cases of childhood nephrotic syndrome which required renal biopsy. METHODS: We retrospectively reviewed the clinical, laboratory, pathologic findings and therapeutic outcomes of 169 nephrotic children who received a renal biopsy at the Department of Pediatrics, Kyunghee Medical University Hospital, Seoul from 1984 to 2004 over a period of 21 years. The renal biopsy was performed in nephrotic children who showed atypical features at presentation, or needed cytotoxic therapy because of frequent-relapsing, steroid-dependent, or steroid-resistant nephrotic syndrome(SRNS). RESULTS: Minimal change disease(MCD) was found in 52.1% of the patients, followed by diffuse mesangial proliferation(33.1%), focal segmental gomerulosclerosis(5.3%), membranoproliferative glomerulonephritis(2.4%), membranous nephropathy(2.4%), and IgA nephropathy(1.8 %). In MCD children, 14.8% had hematuria, 22.7% had hypertension, 5.7% showed decreased renal function, and no patient was found to have an abnormal complement level. Among patients diagnosed with diseases other than MCD, 43.2% had hematuria, 21.0% was found to be hypertensive, 7.4% of children showed decreased renal function and only 3(3.7%) had decreased complement level; the rates of hematuria and SRNS were found to be significantly higher than MCD patients. Among 37 SRNS patients, 30(81.0%) showed a final remission state with long-term steroid therapy, including methylprednisolone pulse therapy, over 4 months, with or without cytotoxic therapy. CONCLUSION: Almost half of the cases of childhood nephrotic syndrome requiring renal biopsy were not diagnosed with MCD. Among atypical features, hematuria and steroid-resistance would be the most probable indicators for a diagnosis other than MCD. Even in patients with SRNS, long-term methylprednisolone pulse therapy may result in a good remission rate.

The Association of Neonatal Hyperbilirubinemia with UGT1A1 and CYP1A2 Gene Polymorphism in Korean Neonates / 소아과

PURPOSE: The incidence of nonphysiologic neonatal hyperbilirubinemia is twice as high in East Asians as in whites. Recently, UGT1A1 mutation was found to be a risk factor for neonatal hyperbilirubinemia. In congenitally-jaundiced Gunn rats, which lack expression of UDP-glucuronosyltransferase, alternative pathways can be stimulated by inducers of CYP1A1 and CYP1A2 enzymes. CYP1A2 plays a major role in bilirubin degradation of the alternate pathway. We studied the relationship between UGT1A1 and CYP1A2 gene polymorphism of neonatal hyperbilirubinemia in Koreans. METHODS: Seventy-nine Korean full term neonates who had hyperbilirubinemia(serum bilirubin >12 mg/dL) without obvious causes of jaundice, were analyzed for UGT1A1 and CYP1A2 gene polymorphism; the control group was sixty-eight. We detected the polymorphism of Gly71Arg of UGT1A1 gene by direct sequencing and T2698G of CYP1A2 by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) using MboII and direct sequencing. RESULTS: Allele frequency of Gly71Arg mutation in the hyperbilirubinemia group was 32 percent, which was significantly higher than 11 percent in the control group(P<0.0001). Mutant gene frequency of T2698G was 41.8 percent in patients and 32.3 percent in the control group(P=0.015), but allele frequency was 21 percent in patients and 19 percent in the control group, which was not significantly higher(P=0.706). There was no relationship between mutations of two genes(P=0.635). CONCLUSION: The polymorphism of UGT1A1 gene(Gly71Arg) and CYP1A2 gene(T2698G) was detected in Korean neonatal hyperbilirubinemia. Only polymorphisms of Gly71Arg in UGT1A1 were significantly higher than control group.