Ja Seol Koo

Genome-wide association study of Crohn's disease in Koreans revealed three new susceptibility loci and common attributes of genetic susceptibility across ethnic populations

Objective Crohns disease (CD) is an intractable inflammatory bowel disease (IBD) of unknown cause. Recent meta-analysis of the genome-wide association studies (GWAS) and Immunochip data identified 163 susceptibility loci to IBD in Caucasians, however there are limited studies in other populations. Methods We performed a GWAS and two validation studies in the Korean population comprising a total of 2311 patients with CD and 2442 controls. Results We confirmed four previously reported loci: TNFSF15, IL23R, the major histocompatibility complex region, and the RNASET2-FGFR1OP-CCR6 region. We identified three new susceptibility loci at genome-wide significance: rs6856616 at 4p14 (OR=1.43, combined p=3.60×10−14), rs11195128 at 10q25 (OR=1.42, combined p=1.55×10−10) and rs11235667 at 11q13 (OR=1.46, combined p=7.15×10−9), implicating ATG16L2 and/or FCHSD2 as novel susceptibility genes for CD. Further analysis of the 11q13 locus revealed a non-synonymous single nucleotide polymorphism (SNP) (R220W/rs11235604) in the evolutionarily conserved region of ATG16L2 with stronger association (OR=1.61, combined p=2.44×10−12) than rs11235667, suggesting ATG16L2 as a novel susceptibility gene for CD and rs11235604 to be a potential causal variant of the association. Two of the three SNPs (rs6856616 (p=0.00024) and rs11195128 (p=5.32×10−5)) showed consistent patterns of association in the International IBD Genetics Consortium dataset. Together, the novel and replicated loci accounted for 5.31% of the total genetic variance for CD risk in Koreans. Conclusions Our study provides new biological insight to CD and supports the complementary value of genetic studies in different populations.

Efficacy, safety, and predictors of response to infliximab therapy for ulcerative colitis: A Korean multicenter retrospective study

Infliximab is currently used for the treatment of moderate‐to‐severe ulcerative colitis (UC) with an inadequate response to conventional agents. The efficacy and safety of infliximab in Korean patients with UC were assessed.

Comparative study of helicobacter pylori eradication rates with 5-day quadruple concomitant therapy and 7-day standard triple therapy

Background: Several studies have shown the superiority of concomitant quadruple therapy containing 3 antibiotics over triple therapy for Helicobacter pylori infection. The aim of this study was to compare concomitant quadruple therapy with standard triple therapy for first-line H. pylori eradication. Methods: A total of 270 patients with proven H. pylori infection were randomly assigned to one of 2 regimens: amoxicillin 1000 mg with clarithromycin 500 mg and lansoprazole 30 mg twice daily for 7 days (triple therapy) or amoxicillin 1000 mg with clarithromycin 500 mg, metronidazole 500 mg, and lansoprazole 30 mg twice daily for 5 days (concomitant therapy). The success of eradication was evaluated 4 to 5 weeks after completion of treatment. Results: Eradication rates were 86.1% in the triple therapy and 91.4% in the concomitant therapy (per protocol), but the difference was not statistically significant. Mild adverse events were more frequently reported in the concomitant-therapy group (35.6%) than in the triple-therapy group (25.2%) (P=0.09). Conclusions: Five-day quadruple concomitant therapy eradicated H. pylori in over 90% of patients. Accordingly, concomitant therapy is thought to be a promising alternative to triple therapy as a first-line treatment regimen for H. pylori eradication.

Immunochip Analysis Identification of 6 Additional Susceptibility Loci for Crohn's Disease in Koreans

Background:Crohns disease (CD) is an intractable inflammatory bowel disease of unknown cause. Recent genome-wide association studies of CD in Korean and Japanese populations suggested marginal sharing of susceptibility loci between Caucasian and Asian populations. As the 7 identified loci altogether explain 5.31% of the risk for CD, the objective of this study was to identify additional CD susceptibility loci in the Korean population. Methods:Using the ImmunoChip custom single-nucleotide polymorphism array designed for dense genotyping of 186 loci identified through GWAS, we analyzed 722 individuals with CD and 461 controls for 96,048 SNP markers in the discovery stage, followed by validation in an additional 948 affected individuals and 977 controls. Results:We confirmed 6 previously reported loci in Caucasian: GPR35 at 2q37 (rs3749172; P = 5.30 × 10−11, odds ratio [OR] = 1.45), ZNF365 at 10q21 (rs224143; P = 2.20 × 10−9, OR = 1.38), ZMIZ1 at 10q22 (rs1250569; P = 3.05 × 10−7, OR = 1.30), NKX2-3 at 10q24 (rs4409764; P = 7.93 × 10−8, OR = 1.32), PTPN2 at 18p11 (rs514000; P = 9.00 × 10−8, OR = 1.33), and USP25 at 21q11 (rs2823256; P = 2.49 × 10−7, OR = 1.35), bringing the number of known CD loci (including 3 in the HLA) in Koreans to 15. The 6 additional loci increased the total genetic variance for CD risk from 5.31% to 7.27% in Koreans. Conclusions:Although the different genetic backgrounds of CD between Asian and Western countries has been well established for the major susceptibility genes, our findings of overlapping associations offer new insights into the genetic architecture of CD.

Endovascular Management for Isolated Spontaneous Dissection of the Superior Mesenteric Artery: Report of Two Cases and Literature Review

The clinical course and treatment strategies of isolated superior mesenteric artery (SMA) dissection have not been fully investigated. Two cases of uncontrolled abdominal pain caused by isolated SMA dissection were successfully treated with percutaneous endovascular stent placement. At follow-up 6 months later, computed tomography confirmed that the lesions had stabilized. The patients remained symptom free at 14- and 13-month follow-up, respectively. The present report describes these two cases of isolated SMA dissection treated successfully with percutaneous endovascular stent placement, along with a review of the related literature.

Patients with Crohn's disease on anti-tumor necrosis factor therapy are at significant risk of inadequate response to the 23-valent pneumococcal polysaccharide vaccine

BACKGROUND/AIMS The effect of immunosuppressants on the efficacy of a variety of vaccines is a controversial issue in patients with inflammatory bowel disease (IBD). In this study we determined whether specific immunosuppressants impair the serological response to the standard 23-valent pneumococcal polysaccharide vaccine (PPSV23) in a large cohort of patients with Crohns disease (CD). METHODS This was a multi-center, prospective observational study of adult patients with CD at 15 academic teaching hospitals in Korea. The study population received one intramuscular injection of PPSV23. Anti-pneumococcal IgG antibody titers were measured by immunoassay prior to and 4weeks after vaccination. All vaccination-related adverse events and the effect of the vaccine on disease activity were also evaluated. RESULTS The overall serological response rate was 67.5% (133/197). The serological response rate was significantly lower in patients on anti-tumor necrosis factor (anti-TNF) therapy (50.0% on anti-TNF alone; 58.0% on anti-TNF combined with an immunomodulator, IM) than patients on 5-aminosalicylate (78.4%; all P-values vs. 5-aminosalicylate<0.05); 45.6% (41/90) of patients on anti-TNF therapy were not protected against PPSV23. IM did not affect the immunologic response to the vaccine. Female gender and anti-TNF therapy were significant predictors of non-response to the vaccine (odds ratio [OR] 2.316, P=0.015; OR 2.582, P=0.048, respectively). Vaccination was generally safe and tolerated by all patients. CONCLUSIONS Patients with CD on anti-TNF therapy are at significant risk of an inadequate response to PPSV23. The pneumococcal vaccination strategy should be optimized for patients with CD on anti-TNF therapy.

Incidences of Serious Infections and Tuberculosis among Patients Receiving Anti-Tumor Necrosis Factor-α Therapy

Purpose Anti-tumor necrosis factor-alpha (TNF-α) medications represent a major advancement in the management of chronic inflammatory diseases. However, these agents are associated with increased risks of tuberculosis (TB) and other serious infections. The aim of this study was to evaluate the incidences of such disease among tertiary hospitals in Korea. Materials and Methods We retrospectively studied patients who received anti-TNF-α therapy; we reviewed serious infections including TB that developed within 6 months after initiation of anti-TNF-α therapy. Data concerning patient demographics, types of anti-TNF-α agents, concomitant immunosuppressive drugs use, and infection details were collected. Results A total 175 patients treated with infliximab (n=72) or adalimumab (n=103) with the following conditions were enrolled: Crohns disease, 34 (19.4%); ulcerative colitis, 20 (11.4%); ankylosing spondylitis, 82 (46.9%); and rheumatoid arthritis, 39 (22.2%). There were 18 cases (6.0%) of serious infections. The most common site of serious infection was the intra-abdomen (n=6), followed by TB (n=3), skin and soft tissue (n=3), bone and joints (n=2), ocular neurons (n=2), lower respiratory tract (n=1), and urinary tract (n=1). Of the 175 patients, only 3 cases showed development of TB. Furthermore, of all those who developed TB, none had taken anti-TB chemoprophylaxis prior to treatment with an anti-TNF agent due to negative screening results. Conclusion Serious infections with anti-TNF-α therapy were uncommon among tertiary hospitals in Korea; TB was the second most frequent infection. Nevertheless, there were no TB reactivations after anti-TB chemoprophylaxis. Accordingly, physicians should be aware of TB in subjects undergoing anti-TNF-α therapy, especially in countries with a high prevalence of TB.

Effectiveness of three times daily lansoprazole/amoxicillin dual therapy for Helicobacter pylori infection in Korea.

AIM We compared three times daily dual therapy with standard triple therapy for effectiveness and safety in H. pylori infection. METHODS Two hundred and four H. pylori positive patients with peptic ulcer were randomly assigned to one of two regimens: (i) triple therapy with amoxicillin, clarithromycin and lansoprazole twice daily for 2 weeks or (ii) dual therapy with amoxicillin and lansoprazole three times daily for 2 weeks. The success of eradication was evaluated 4 to 5 weeks after completing treatment. RESULTS The eradication rate was 82.8% in the triple therapy group and 78.4% in the dual therapy group by per protocol analysis. This difference was not significant (P= 0.573). Adverse events were more frequent in the triple therapy group than in the dual therapy group (P= 0.002). CONCLUSIONS Because dual therapy had fewer side effects than triple therapy and a similar eradication rate, dual therapy may provide an acceptable alternative first line therapy for H. pylori eradication in Korea.

Helicobacter pylori recurrence after first- and second-line eradication therapy in Korea: the problem of recrudescence or reinfection.

Recurrence of Helicobacter pylori (H. pylori) infection is the result of either recrudescence or reinfection. Annual recurrence rates per patient‐year of follow‐up have been reported to vary across countries. The aim of this study was to analyze recurrence rates of H. pylori after first‐line and second‐line eradication therapies in Korea.

Effectiveness and safety of repeated quadruple therapy in Helicobacter pylori infection after failure of second-line quadruple therapy: repeated quadruple therapy as a third-line therapy.

Backgrounds:  Quadruple therapy using a proton‐pump inhibitor, bismuth, metronidazole, and tetracycline is a standard second‐line therapy for Helicobacter pylori infection, achieving an eradication rate of about 80% in Korea. A standard third‐line therapy is not currently established, although various protocols have been proposed. We performed this study to evaluate the effectiveness of a retrial with quadruple therapy before starting a third‐line treatment with new drugs.