Trans-ethnic meta-analysis of genome-wide association studies for Hirschsprung disease.

Hirschsprung disease (HSCR) is the most common cause of neonatal intestinal obstruction. It is characterized by the absence of ganglia in the nerve plexuses of the lower gastrointestinal tract. So far, three common disease-susceptibility variants at the RET, SEMA3 and NRG1 loci have been detected through genome-wide association studies (GWAS) in Europeans and Asians to understand its genetic etiologies. Here we present a trans-ethnic meta-analysis of 507 HSCR cases and 1191 controls, combining all published GWAS results on HSCR to fine-map these loci and narrow down the putatively causal variants to 99% credible sets. We also demonstrate that the effects of RET and NRG1 are universal across European and Asian ancestries. In contrast, we detected a European-specific association of a low-frequency variant, rs80227144, in SEMA3 [odds ratio (OR) = 5.2, P = 4.7 × 10-10]. Conditional analyses on the lead SNPs revealed a secondary association signal, corresponding to an Asian-specific, low-frequency missense variant encoding RET p.Asp489Asn (rs9282834, conditional OR = 20.3, conditional P = 4.1 × 10-14). When in trans with the RET intron 1 enhancer risk allele, rs9282834 increases the risk of HSCR from 1.1 to 26.7. Overall, our study provides further insights into the genetic architecture of HSCR and has profound implications for future study designs.

Potential association between ITPKC genetic variations and Hirschsprung disease.

Hirschsprung disease (HSCR) is a congenital and complex disorder characterized by intestinal obstruction due to the absence of enteric neurons along variable lengths of the hindgut. Our recent genome-wide association study (GWAS) has revealed regional associations with HSCR at several loci of inositol-trisphosphate 3-kinase C (ITPKC). For fine mapping, we additionally selected and genotyped a total of 12 single nucleotide polymorphisms (SNPs) of ITPKC in 187 HSCR patients and 283 unaffected controls, and performed a further combined imputation analysis based on genotype data from this second stage of fine mapping and our previous GWAS stage, totaling 902 subjects (187 HSCR cases and 715 controls). As a result, several SNPs (minimum P = 0.004) and a haplotype (P = 0.02) were found to be significantly associated with HSCR. In further in silico analyses to ascertain the potential functions of the significant variants, the change from the common allele to the rare allele of the highly conserved nonsynonymous rs76785336 showed a difference in mRNA folding structure. In the case of intronic SNPs, rs2607420 with a high consensus value was predicted to be a new splice site. Although this study has limitations (such as lack of functional evaluations, small number of cases, and further need of replication in other cohorts), our findings suggest that genetic variants of ITPKC may have a potential association with HSCR susceptibility and/or developmental diseases related to enteric nervous system development.

Association Analysis of SLC6A20 Polymorphisms With Hirschsprung Disease.

PURPOSE: Hirschsprung disease (HSCR) is a congenital and heterogeneous disorder, which is caused by no neuronal ganglion cells in part or all of distal gastrointestinal tract. Recently, our genome-wide association study has identified solute carrier family 6, proline IMINO transporter, member 20 (SLC6A20) as one of the potential risk factors for HSCR development. This study performed a replication study for the association of SLC6A20 polymorphisms with HSCR and an extended analysis to investigate further associations for subgroups and haplotypes. METHODS: For the replication study, a total of 40 single nucleotide polymorphisms (SNPs) of SLC6A20 were genotyped in 187 HSCR subjects composed of 121 short-segment HSCR, 45 long-segment HSCR (L-HSCR), 21 total colonic aganglionosis, and 283 unaffected controls. Imputation was performed using genotype data from our genome-wide association study and this replication study. RESULTS: Imputed meta-analysis revealed that 13 SLC6A20 SNPs (minimum P = 0.0002 at rs6770261) were significantly associated with HSCR even after correction for multiple comparisons using false discovery rate (FDR) (minimum PFDR =  .005). In further subgroup analysis, SLC6A20 polymorphisms appeared to have increased associations with L-HSCR. Moreover, haplotype analysis also showed significant associations between 2 haplotypes (BL3_ht2 and BL4_ht2) and HSCR susceptibility (PFDR <  .05). CONCLUSIONS: Although further replications and functional evaluations are required, our results suggest that SLC6A20 may have roles in HSCR development and in the extent of aganglionic segment during enteric nervous system development.

The randomized crossover comparison of airway sealing with the laryngeal mask airway Supreme(™) at three different intracuff pressures in children.

BACKGROUND: An intracuff pressure of 80 cm H2 O in the adult-sized laryngeal mask airway Supreme has been recommended to obtain a higher oropharyngeal leak pressure (OLP). However, the intracuff pressure for the higher OLP in the pediatric laryngeal mask airway Supreme could be different from that in the adult-sized laryngeal mask airway Supreme. Thus, we measured and compared OLP at three intracuff pressures of 40, 60, and 80 cm H2 O in the pediatric laryngeal mask airway Supreme. METHODS: This study was designed as a randomized crossover study and enrolled 36 children, aged 0-108 months and 5-30 kg in weight. After insertion of the laryngeal mask airway Supreme, oropharyngeal leak pressure (OLP) was measured at intracuff pressures of 40, 60, and 80 cm H2 O according to one of six sequences produced on the basis of 3 × 6 Williams crossover design. During the intraoperative period, the laryngeal mask airway Supreme was maintained using the last intracuff pressure of the allocated sequence. The intraoperative and postoperative complications were compared among three maintenance intracuff pressures. RESULTS: OLP at the intracuff pressure of 60 cm H2 O was significantly higher than that of 40 cm H2 O (17.9 ± 3.9 vs 16.9 ± 4.2 cm H2 O, P = 0.004) and was comparable with that of 80 cm H2 O (17.9 ± 3.9 vs 17.8 ± 4.6 cm H2 O, P = 0.938). There were no significant differences of intraoperative and postoperative complications among the three maintenance intracuff pressures. CONCLUSION: Our results suggest that the use of an intracuff pressure of 60 cm H2 O in pediatric laryngeal mask airway Supreme provides a higher OLP compared with 40 cm H2 O.

Comparison of 2 cuff inflation methods before insertion of laryngeal mask airway for safe use without cuff manometer in children.

PURPOSE: This prospective, randomized trial was conducted to establish whether the pediatric laryngeal mask airway (LMA) could be used without any concerns for abnormally high intra-cuff pressure when a cuff of the LMA was inflated with half the maximum recommended inflation volume or the resting volume before insertion. BASIC PROCEDURES: Eighty children 0 to 9 years of age and weighing of 5 to 30 kg scheduled for general anesthesia were included. Before insertion, the cuff of the LMA was filled with half the maximum recommended inflation volume in the Half volume group, or the resting volume by opening the pilot balloon valve to atmospheric pressure in the Resting volume group. After insertion of the LMA, intra-cuff pressure, oropharyngeal leak pressure, and leakage volume were investigated. MAJOR FINDINGS: The Half volume group showed lower mean intra-cuff pressure than the Resting volume group (49.6 ± 12.1 cm H(2)O vs 58.1 ± 13.8 cm H(2)O, P = .005). There was no difference in oropharyngeal leak pressure (22.1 ± 5.8 vs 21.7 ± 5.1 cm H(2)O, P = .757) or leakage volume between the Half volume group and the Resting volume group (0.13 ± 0.13 ml/kg vs 0.11 ± 0.12 ml/kg, P = .494) under spontaneous respiration. CONCLUSIONS: Both methods of the LMA cuff inflation before insertion provided an acceptable range of intra-cuff pressure with adequate pharyngeal sealing without any intervention after insertion.

Second serial transverse enteroplasty procedure in an infant with extreme short bowel syndrome.

The serial transverse enteroplasty (STEP) procedure is a novel technique to lengthen and taper the bowel in patients with short bowel syndrome. The advantages of STEP include not only technical ease and simplicity, but also the ability to repeat the procedure. Herein, we report a case of extreme short bowel syndrome that was successfully treated by the second STEP procedure. A 3-day old newborn girl underwent STEP because of jejunal atresia with the small bowel length of 15 cm, but her bowel elongation was not enough to escape from short bowel syndrome. At the age of 6 months, she underwent a second STEP procedure. The bowel lengthening by the second STEP made her tolerable to enteral feeding with body weight gain and rescued her from short bowel syndrome. This case showed that second STEP is very helpful in treatment of extreme short bowel syndrome.

Internal jugular vein deformities after central venous catheterisation in neonates: evaluation by Doppler ultrasound.

AIM: The use of a central venous catheter (CVC) through the internal jugular vein (IJV) in neonates is associated with various complications. We postulated that the risk of vein deformity after removing the CVC is underestimated. This study aimed to evaluate, using Doppler ultrasound, morphological changes in the IJV that had undergone CVC insertion during the neonatal period. METHODS: The study consisted of 23 cases, in which 2.7 Fr Broviac (Bard Access Systems, Salt Lake City, Utah, USA) CVCs were inserted through the IJVs of newborns over a 2-year period. After the removal of the CVCs, the IJVs were examined by Doppler ultrasound. RESULTS: Seventeen cases had normal appearances, but six (26%) cases had deformities. One case had a completely obstructed IJV, and five had abnormal compressibility, echogenic intravascular masses or monophasic waveforms of blood flow. On follow-up, IJV deformities were not improved but tended to be aggravated. There were significant differences in gestational age (36.6 +/- 3.2 weeks vs. 30.0 +/- 3.9 weeks, P= 0.002), body weight at time of CVC insertion (2.60 +/- 0.72 kg vs. 1.32 +/- 0.47 kg, P= 0.001) and duration of catheter use (25.9 +/- 13.6 days vs. 49.0 +/- 22.0 days, P= 0.016) between the normal and deformity groups, respectively. CONCLUSIONS: IJV deformities after central venous catheterisation in neonates are common. A lower gestational age, a lower body weight, and more catheter indwelling days are significant factors affecting the incidence of IJV deformities.

Clinical characteristics and conservative treatment of perineal groove.

PURPOSE: Perineal groove is a rare congenital anomaly of the perineum, and only a few papers describing a small number of cases have been reported in the medical literature. This study aimed to evaluate the clinical characteristics and proper management of perineal groove. METHODS: We performed a retrospective review of 26 pediatric patients who were diagnosed with perineal groove between January 2012 and October 2018 at our institution. RESULTS: Perineal groove was extremely prevalent among the females: 25 of the 26 patients were girls, and only one patient was a boy. All the patients presented with an unusual lesion at the anus or perineum, but no symptoms related to this anomaly. The median age at the first visit to our clinic was 1.5 month (range, 0.3-11.4 month). Two types, complete and partial, were used to categorize the appearance of perineal groove. In a sample group, 55% (12/22) of the patients had complete perineal groove while 45% (10/22) had partial perineal groove. One patient underwent an anoplasty at another hospital following the diagnosis of an imperforate anus. One male and 13 female patients were followed beyond the age of two, and 10 patients (71%) showed a natural healing process. CONCLUSION: Perineal groove manifested as two types of appearance and showed excellent results with conservative treatment in our study. A natural healing process can be expected in the long-term follow-up. Perineal groove must be differentiated from other defects to avoid unnecessary surgical treatment. LEVELS OF EVIDENCE: Therapeutic Study, Level IV.

Biliary atresia: color doppler US findings in neonates and infants.

PURPOSE: To describe color Doppler ultrasonographic (US) findings in livers of neonates with biliary atresia (BA) and to compare them with US findings in livers of neonates with non-BA and control subjects. MATERIALS AND METHODS: Institutional review board approval was obtained; acquisition of informed consent was exempted. US and color Doppler US findings were retrospectively reviewed in 64 patients with neonatal cholestasis and 19 control subjects. BA and non-BA were confirmed in 29 and 35 patients, respectively. Three pediatric radiologists assessed US and color Doppler US images, independently documented their findings, and resolved discrepancies by consensus. Triangular cord (TC) sign, gallbladder length, and hepatic artery and portal vein diameters were evaluated on US images. The presence of hepatic subcapsular flow was evaluated on color Doppler US images. Diagnostic value of TC sign and hepatic subcapsular flow in the diagnosis of BA were evaluated. Significance of hepatic artery and portal vein diameters in each group was assessed. RESULTS: In the diagnosis of BA, sensitivity and specificity of the TC sign on US images were 62% and 100%, respectively. On color Doppler US images, hepatic subcapsular flow was detected in all patients with BA and in five patients with non-BA. At the first review, there was a discrepancy between radiologists in interpretation of hepatic subcapsular flow in patients with non-BA. However, consensus was reached at the second review. There was no hepatic subcapsular flow in control subjects. Sensitivity and specificity of hepatic subcapsular flow on color Doppler US images were 100% and 80%-86%, respectively, on the basis of individual interpretations of reviewers. Sensitivity and specificity of hepatic subcapsular flow on color Doppler US images were 100% and 86%, respectively, on the basis of consensus reading. Mean diameter of the hepatic artery in patients with BA (2.1 mm +/- 0.7 [standard deviation]) was significantly larger than that in patients with non-BA (1.5 mm +/- 0.4, P < .001) and control subjects (1.5 mm +/- 0.4, P = .001). CONCLUSION: The presence of hepatic subcapsular flow is useful for differentiating between BA and other causes of neonatal jaundice.

Hepatic fibrosis scan for liver stiffness score measurement: a useful preendoscopic screening test for the detection of varices in postoperative patients with biliary atresia.

OBJECTIVE: Even after successful Kasai portoenterostomy, progressive hepatic fibrosis in postoperative patients with biliary atresia (BA) can be associated with portal hypertension and esophageal or gastric varices. Therefore, early diagnosis and close follow-up of varices are important. We investigated the correlation between the liver stiffness scores measured by FibroScan and the presence of esophageal or gastric varices to examine the usefulness of FibroScan as a preendoscopic screening test for varices. PATIENTS AND METHODS: A total of 49 of 81 children with BA following successful Kasai operations were enrolled in this study. FibroScan and endoscopic examination were performed prospectively. RESULTS: There were 22 males (44.9%) and the mean age of the patients was 3.8 +/- 2.7 years. Esophageal or gastric varices were present in 30 patients (Vx group) and absent in 19 (nVx group). The mean liver stiffness score was significantly higher in the Vx group (21.35 +/- 10.31 kPa in the Vx group versus 9.75 +/- 8.61 kPa in the nVx group, P < 0.001). The optimal cutoff value of the liver stiffness score for the prediction of a varix was 9.7 kPa with a sensitivity of 0.97 and a specificity of 0.80. CONCLUSIONS: Liver stiffness scores measured by FibroScan correlate well with the presence of esophageal or gastric varices. FibroScan is a novel, noninvasive, and useful screening method for the preendoscopic detection of varices in postoperative patients with BA.

Potential association between TSGA13 variants and risk of total colonic aganglionosis in Hirschsprung disease.

Hirschsprung disease (HSCR) is a congenital rare disorder and a kind of developmental neuropathies, characterized by the lack of enteric neurons in variable segments of distal bowel. Our recent genome-wide association study identified a variant (rs13223150) of testis-specific A13 (TSGA13) as a potential risk locus for total colonic aganglionosis (TCA) in HSCR. The aim of this study was to identify the impact of the variant (rs13223150) and potential association of genetic variations of TSGA13 with TCA in HSCR. This study performed a fine mapping and extended analyses in Korean population. A total of 9 single nucleotide polymorphisms (SNPs) of TSGA13 were genotyped in a larger HSCR cohort (187 HSCR patients and 283 unaffected controls), and extended genetic analyses using various genetic modelling, haplotype, and combined analyses were performed. The rs13223150_A allele showed a significant association with TCA (P = 0.003), even after correcting for multiple testing (Pcorr = 0.02). One haplotype (BL1_ht1, G-A-C-C) including rs13223150 also showed a significant association with TCA (P = 0.002, Pcorr = 0.01). Further combined imputation analysis indicated that several single nucleotide polymorphisms of TSGA13 were significantly associated with TCA in HSCR. Although replications in other population cohorts and functional evaluations are needed, our results suggest that TSGA13 genetic variants may affect TCA in HSCR and/or the extent of aganglionosis during enteric nervous system development.

Association analysis of NOX5 polymorphisms with Hirschsprung disease.

BACKGROUND/PURPOSE: Hirschsprung disease (HSCR) is a developmental disease characterized by the absence of ganglion cells in the intestinal region. NADPH oxidase5 (NOX5) has been identified as one of the possible candidate genes for risk of Hirschsprung disease in our recent genome wide association study (GWAS). In this study, we performed a replication study to analyze the association of NOX5 polymorphisms with HSCR risk and conducted an extended analysis to investigate further associations for sub-groups and haplotypes. METHODS: A total of 23 NOX5 single nucleotide polymorphisms (SNPs) were genotyped in 187 HSCR patients and 283 unaffected controls. Statistical analysis was performed to examine the effects of genotype on risk of HSCR and HSCR subtype. RESULTS: Logistic regression analyses revealed that six SNPs (rs59355559, rs62010828, rs34990910, rs11856030, rs311905, and rs8024894) were associated with risk of HSCR (minimum p = 0.007 at rs62010828). Moreover, three SNPs (rs59355559, rs62010828, and rs8024894) were significantly associated with risk of long-segment HSCR (L-HSCR) subtype and 5 SNPs (rs59355559, rs62010828, rs34990910, rs11856030, and rs8024894) were found to be associated with risk of TCA subtype. CONCLUSION: Our results demonstrate that genetic variants in NOX5 have genetic effects on risk of HSCR, which may serve as useful preliminary information for further study. LEVELS OF EVIDENCE: Level III of prognosis study.

Laparoscopic repair of inguinal hernia in infants: Comparison with open hernia repair.

PURPOSE: This study aimed to evaluate the usefulness of laparoscopic repair of inguinal hernia (LR) in infants in comparison with open hernia repair (OR). METHODS: We retrospectively analyzed the clinical data of 465 infants treated for inguinal hernia from January 2006 to December 2015. Among them, 124 underwent LR and 341 underwent OR. RESULTS: In the OR group, 16.1% (55/341) primarily underwent bilateral inguinal hernia repair and 13.6% (42/308) subsequently developed metachronous contralateral inguinal hernia during follow-up. In the LR group, 75.8% (94/124) underwent primary bilateral inguinal hernia repair and only 1.6% (2/123) developed metachronous contralateral inguinal hernia. The mean operation times of unilateral inguinal hernia repair showed no statistical differences between LR and OR. However, the mean operation times of bilateral inguinal hernia repair were shorter in LR (39.8±10.4 vs. 51.1±14.4min, p<0.001). Postoperative recurrence and wound infection showed no statistical differences between the groups, but postoperative scrotal swelling was more common in OR (0.0% vs. 4.0%, p=0.006). CONCLUSION: LR in infants showed a lower incidence of metachronous hernia, shorter operation times, and better postoperative course than OR. LR could be considered the primary operation method in infants with inguinal hernia. LEVELS OF EVIDENCE: Prognosis Study, Retrospective Study, Level III.

Urachal anomalies in children: a single center experience.

The objective of this study is to define optimal diagnosis and treatment strategies for patients with urachal anomalies in the pediatric age group. The medical records of 21 children who had undergone surgery for urachal anomalies at Severance Hospital, Yonsei University College of Medicine from January 1990 to April 2005 were reviewed. The subjects included 14 males and 7 females (M:F 2:1). The four types of urachal anomalies confirmed were a urachal cyst in 10 patients (47.6%), a patent urachus in 6 (28.6%), a urachal sinus in 4 (19.0%) and a urachal diverticulum in 1 (4.8%) patient. The most common presenting complaint was umbilical discharge (n = 10, 40.0%), followed by abdominal mass (n = 9, 36.0%). Urachal anomalies were diagnosed by ultrasonography in 18 patients, and 7 of them were additionally examined by computed tomography. The remaining patients were diagnosed solely by surgical exploration. Excision was performed in all patients and was supplemented by partial cystectomy in three. Umbilical discharge was the most common clinical manifestation in our patients, suggesting that ultrasonography should be performed in patients with umbilical discharge to differentiate urachal anomalies. We found the most common anomaly to be the urachal cyst, and all patients were successfully treated by surgical excision.

A genome-wide association analysis of chromosomal aberrations and Hirschsprung disease.

Hirschsprung disease (HSCR) is a neurocristopathy characterized by the absence of intramural ganglion cells along variable lengths of the gastrointestinal tract. Although the RET proto-oncogene is considered to be the main risk factor for HSCR, only about 30% of the HSCR cases can be explained by variations in previously known genes including RET. Recently, copy number variation (CNV) and loss of heterozygosity (LOH) have emerged as new ways to understand human genomic variation. The goal of this present study is to identify new HSCR genetic factors related to CNV in Korean patients. In the genome-wide genotyping, using Illumina's HumanOmni1-Quad BeadChip (1,140,419 markers), of 123 HSCR patients and 432 unaffected subjects (total n = 555), a total of 8,188 CNVs (1 kb âˆ¼ 1 mb) were identified by CNVpartition. As a result, 16 CNV regions and 13 LOH regions were identified as associated with HSCR (minimum P = 0.0005). Two top CNV regions (deletions at chr6:32675155-32680480 and chr22:20733495-21607293) were successfully validated by additional real-time quantitative polymerase chain reaction analysis. In addition, 2 CNV regions (6p21.32 and 22q11.21) and 2 LOH regions (3p22.2 and 14q23.3) were discovered to be unique to the HSCR patients group. Regarding the large-scale chromosomal aberrations (>1 mb), 11 large aberrations in the HSCR patients group were identified, which suggests that they may be a risk factor for HSCR. Although further replication in a larger cohort is needed, our findings may contribute to the understanding of the etiology of HSCR.

Solid-pseudopapillary tumours of the pancreas: 14 years experience.

BACKGROUND: Solid-pseudopapillary tumour of the pancreas (SPTP) is a low-grade malignancy lesion that is distinct from other pancreatic tumours. Preoperative diagnosis is often inaccurate and treatment strategies remain controversial. The present study reviews the clinical features, diagnosis, treatment, and outcome of Asian patients with SPTP from a single institution. METHODS: The medical records and images of patients who underwent surgery for SPTP between June 1990 and December 2003 were retrospectively reviewed. Study eligibility required that patients had undergone surgical resections and that the SPTP had been pathologically demonstrated. RESULTS: Twenty-eight patients with SPTP were identified. Eighteen patients (64.3%) reported the predominant symptom of 'vague abdominal pain', five patients (17.8%) had an apparent 'abdominal mass', and five patients (17.8%) without overt symptoms had masses that were discovered incidentally during screening. All patients underwent magnetic resonance (MR) imaging (n = 22) and/or computed tomography (n = 17), with a specificity of 90.9% and 76.4%, respectively. All masses were well-circumscribed, except for a tumour in one patient (3.6%), which adhered to the stomach wall and metastasized to the liver. Two patients (7.1%) underwent enucleation, while 25 patients (89.3%) received curative resection. The patient with the liver metastases underwent distal pancreatectomy and splenectomy with partial hepatectomy. The mean follow up was 66.9 months. No mortality occurred during follow up but the patient with the liver metastasis had progressive deterioration. CONCLUSION: Symptoms of SPTP are indistinct and preoperative diagnosis is often inaccurate. Magnetic resonance imaging improves SPTP diagnosis. In general, the prognosis of well-circumscribed SPTP is favourable after curative resection.

Ultrasonographic assessment of optic nerve sheath diameter during pediatric laparoscopy.

This study investigated the extent of the raised intracranial pressure resulting from carbon dioxide (CO2) pneumoperitoneum by ultrasonographically measuring optic nerve sheath diameter (ONSD) in children undergoing laparoscopic surgery. Twenty-five children aged less than 9 y (53.1 ± 23.3 mo, mean ± standard deviation) and scheduled for an elective laparoscopic surgery participated. ONSD was assessed using ocular ultrasonography 10 min after induction of anesthesia (T0), 10 min after induction of CO2 pneumoperitoneum at 10 mm Hg intra-abdominal pressure (T1) and in an anesthetized state without CO2 pneumoperitoneum at the conclusion of the surgery (T2). During CO2 pneumoperitoneum, ONSD increased significantly compared with ONSD after anesthesia induction (T0: 4.3 ± 0.3 mm, T1: 4.6 ± 0.3 mm, p < 0.05). In all enrolled patients, any neurologic complications were not observed during the intra-operative or post-operative period. In children undergoing laparoscopic surgery, an increase in ONSD was ascertained during CO2 pneumoperitoneum, and thus the corresponding increase in intracranial pressure could be predicted.

Potential Association of INMT Nonsynonymous Variant (His46Pro) with Hirschsprung's Disease.

BACKGROUND: Hirschsprung's disease (HSCR) is a congenital disorder which is characterized by the lack of ganglion cells in part of or the entire colon, resulting in intestinal obstruction and other related symptoms. Recently, our group has conducted a genome-wide association study in Korean HSCR cases and controls to identify novel markers in other genes. OBJECTIVES: The present research aimed to further study the potential association of INMT with HSCR by conducting a replication study. METHODS: A total of 15 INMT single nucleotide polymorphisms (SNPs) were analyzed for the association with HSCR in 187 HSCR patients and 283 controls. Analyses were also conducted for subtypes of HSCR (short-segment, long-segment, and total colonic aganglionosis). RESULTS: A nonsynonymous SNP rs77743549 (His46Pro) was significantly associated with the increased risk of HSCR (odds ratio = 1.77; corrected p = 0.002). Furthermore, this rs77743549 retained its association with all subtypes of HSCR (p = 0.006-0.002 under the codominant model). A global test showed that rs77743549 was associated with the length of aganglionosis (p = 0.00004). CONCLUSION: Although further replications and functional evaluations are needed, our study suggests that rs77743549 of INMT may be associated with the risk for HSCR and/or the development of the enteric nervous system.

A comprehensive karyotypic analysis on Korean hepatocellular carcinoma cell lines by cross-species color banding and comparative genomic hybridization.

Chromosomal aberrations were investigated in hepatitis B virus integrated into the hepatocellular carcinoma (HCC) cell lines SNU-368, SNU-449, SNU-398, SNU-182, and SNU-475 using Giemsa-banding, cross species color banding, and comparative genomic hybridization (CGH). The origins of the marker chromosomes were confirmed by fluorescence in situ hybridization with constructed chromosome painting probes. Each cell line had unique modal karyotypic characteristics and showed variable numbers of numerical and structural clonal cytogenetic aberrations. The gains were commonly detected on chromosome 1, and chromosome regions 6p, 7q, 8q, 10p, 17q, and 20; the losses were often found on 4q21 approximately qter, 13, 18q21 approximately qter, and Y. In particular, the breakpoints on 1p36, 1p13 approximately q21, 2p13 approximately q11, 6q10 approximately q11, 7q11, 7q22, 14q10, 16q10 approximately q13, 17q21, 18q21, and 19p11 approximately q11 were involved frequently at the multiple rearranged lesions. CGH analysis further confirmed the cytogenetic data, and the nonrandom rearrangements data suggested the candidate regions for the genes to be isolated which were related to HCC.