A non-synonymous variant rs12614 of complement factor B associated with risk of chronic hepatitis B in a Korean population.

BACKGROUND: Hepatitis B is known to cause several forms of liver diseases including chronic hepatitis B (CHB), and hepatocellular carcinoma. Previous genome-wide association study of CHB risk has demonstrated that rs12614 of complement factor B (CFB) was significantly associated with CHB risk. In this study, fine-mapping study of previously reported GWAS single nucleotide polymorphism (SNP; CFB rs12614) was performed to validate genetic effect of rs12614 on CHB susceptibility and identify possible additional causal variants around rs12614 in a Korean population. This association study was conducted in order to identify genetic effects of CFB single nucleotide polymorphisms (SNPs) and to identify additional independent CHB susceptible causal markers within a Korean population. METHODS: A total of 10 CFB genetic polymorphisms were selected and genotyped in 1716 study subjects comprised of 955 CHB patients and 761 population controls. RESULTS: A non-synonymous variant, rs12614 (Arg32Trp) in exon2 of CFB, had significant associations with risk of CHB (odds ratio = 0.43, P = 5.91 × 10- 10). Additional linkage disequilibrium and conditional analysis confirmed that rs12614 had independent genetic effect on CHB susceptibility with previously identified CHB markers. The genetic risk scores (GRSs) were calculated and the CHB patients had higher GRSs than the population controls. Moreover, OR was found to increase significantly with cumulative GRS. CONCLUSIONS: rs12614 showed significant genetic effect on CHB risk within the Korean population. As such rs12614 may be used as a possible causal genetic variant for CHB susceptibility.

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.

Association analysis of RTEL1 variants with risk of adult gliomas in a Korean population.

Previous studies have identified multiple loci for inherited susceptibility to glioma development, including the regulator of telomere elongation helicase 1 (RTEL1). However, the association between RTEL1 variants and risk of glioma has not been well understood. Therefore, we sought to comprehensively examine the genetic interaction between RTEL1 variants and risk of glioma with respect to defined histological and molecular subtypes. We employed a case-control study involving 250 adult glioma patients with previous molecular alterations and 375 population-based controls within Korean populations. Statistical analyses on the association between RTEL1 single nucleotide polymorphisms (SNPs) and glioma risk were conducted using unconditional logistic regression. Additional conditional and stepwise analyses were performed on significant RTEL1 SNPs. We detected significant associations (Bonferroni P < .05) between six SNPs (rs6089953, rs3848669, rs6010620, rs3787089, rs6062302, and rs115303435) and risk of glioma in the Korean subjects. The two coding variants, rs6062302 (D664D) and rs115303435 (A1059T), were plausibly causal variants and were independent among the significantly associated RTEL1 variants. The glioma subgroup analyses showed that the causal variants (rs6062302 and rs115303435) may be associated with increased risk of glioma regardless of histological grades and molecular alterations. This study provides a deeper understanding of relationships between RTEL1 variants and risk of glioma. Further studies are required to ascertain the impact of those variants on glioma susceptibility.

Genetic association of complement component 2 variants with chronic hepatitis B in a Korean population.

BACKGROUND & AIMS: Numerous single nucleotide polymorphisms associated with an increased risk of liver diseases, chronic hepatitis B and chronic hepatitis B-related hepatocellular carcinoma have been identified. In this study, we scrutinized the genetic effects of C2 variants, which were conflicting in previous results, on the risk of chronic hepatitis B in a Korean population. METHODS: We genotyped 22 common C2 genetic variants of 977 chronic hepatitis B cases including 302 chronic hepatitis B-related hepatocellular carcinoma cases and 785 population controls. Statistical analysis was performed to examine the effects of genotype on the risk of chronic hepatitis B and chronic hepatitis B-related hepatocellular carcinoma. RESULTS: Logistic regression analyses showed that six C2 single nucleotide polymorphisms had significant associations with the risk of chronic hepatitis B and chronic hepatitis B-related hepatocellular carcinoma among the Korean subjects. Stepwise analysis revealed that causal markers (rs9267665 and rs10947223) were identified among the C2 variants (stepwise P = 3.32 × 10-9 and 2.04 × 10-5 respectively). In further conditional analysis with previous chronic hepatitis B-associated loci, these two single nucleotide polymorphisms were independently associated with the risk of chronic hepatitis B. In addition, we investigated the ability of genetic risk scores combining 12 multi-chronic hepatitis B loci to predict the risk of chronic hepatitis B. Individuals with higher genetic risk scores showed increased risk for chronic hepatitis B. CONCLUSIONS: Our results suggested that the C2 gene might be a susceptibility locus for chronic hepatitis B in Korean populations. The cumulative genetic effects may contribute to future etiological explanations for chronic hepatitis B.

Usefulness and safety of endoscopic treatment for nonampullary duodenal adenoma and adenocarcinoma.

BACKGROUND AND AIM: Safety and efficacy data on endoscopic treatment of duodenal neoplasm are limited. We suggest the technical feasibility of endoscopic procedures by evaluating the results of endoscopic treatment for nonampullary duodenal adenoma and adenocarcinoma. METHODS: Forty-five patients who underwent endoscopic treatment for nonampullary duodenal adenoma with or without malignant transformation between September 2003 and March 2012 were included. Endoscopic polypectomy of duodenal polyp (DPP), duodenal endoscopic mucosal resection (DEMR), and duodenal endoscopic submucosal dissection (DESD) were selected as endoscopic treatments for each lesion. RESULTS: Mean lesion size was 9.1 mm, and most lesions were located in the second portion of the duodenum. There were 40 adenomas and five early-stage adenocarcinomas arising from adenomas. Of the 45 duodenal neoplasms, five patients were treated with DPP, 33 with DEMR, and seven patients with a large duodenal lesion underwent DESD. Minimum of 1-year follow-up endoscopies were performed in 42 patients, excepting three patients treated after October 2011. Median follow-up was 24.8 months. Of the 45 patients, en bloc resection was performed in 43 (95.6%). A complete resection was performed in 41 patients (91.1%). No significant bleeding events occurred. Perforations occurred in three patients who underwent DESD. All perforations were noticed during the procedures and completely closed by endoscopic clipping. There was one recurrence at 6 months after DPP. CONCLUSION: Endoscopic treatment is minimally invasive management for duodenal adenomas and superficial adenocarcinomas. It would be helpful for medical doctors in the management of duodenal neoplasms.

[Endoscopic submucosal dissection of a leiomyoma originating from the muscularis propria of upper esophagus].

The technique of endoscopic submucosal dissection is occasionally used for resection of myogenic tumors originating from muscularis mucosa or muscularis propria of stomach and esophagus. However, endoscopic treatments for esophageal myogenic tumors >2 cm have rarely been reported. Herein, we report a case of large leiomyoma originating from muscularis propria in the upper esophagus. A 59-year-old woman presented with dysphagia. Esophagoscopy and endoscopic ultrasonography revealed an esophageal subepithelial tumor which measured 25 × 20 mm in size, originated from muscularis propria, and was located at 20 cm from the central incisors. The tumor was successfully removed by endoscopic submucosal dissection and there were no complications after en bloc resection. Pathologic examination was compatible with leiomyoma.