Association of FUT2 and ABO with Crohn's disease in Koreans.

BACKGROUND AND AIM: Fucosyltransferase 2 (FUT2) at 19q13 is a well-established susceptibility locus for Crohn's disease (CD) in Caucasians. FUT2 encodes α-1,2-fucosyltransferase that regulates the secretion of the α-1-2-N-acetylgalactosaminyltransferase and α-1-3-galactosyltransferase (ABO) antigens in both the gastrointestinal mucosa and secretory glands. Given that CD is thought to arise from dysregulated mucosal immune responses to the gut flora and both the ABO blood group and the FUT2 secretor status affect the composition of the gut microbiota, the goal of this study was to evaluate the associations of variants of FUT2 and ABO with CD in Koreans. METHODS: Three single-nucleotide polymorphisms from the FUT2 and ABO genes were genotyped in 1735 patients with CD and 8074 healthy controls. RESULTS: The FUT2 non-secretor allele showed genome-wide significant association with CD in Koreans (rs1047781, odds ratio [OR] = 1.30, Pcombined  = 3.52 × 10-12 ). The ABO locus showed genome-wide significant association with CD in Asians (Pmeta  = 2.35 × 10-8 ). A moderate association was observed with the A and B groups (OR = 1.40, P = 2.26 × 10-6 ; and OR = 1.32, P = 1.92 × 10-4 , respectively) compared with the O group. Following stratification on the basis of FUT2 genotype, carriers of the secretor O blood group were significantly protective against CD than were those of the secretor non-O blood group (OR = 0.63, 95% confidence interval = 0.54-0.73, P = 2.86 × 10-9 ). CONCLUSIONS: These are the first results indicating that the O blood group and FUT2 secretor status are protective factors against CD in Asians.

Effects of smoking on the association of human leukocyte antigen with ulcerative colitis.

BACKGROUND AND AIM: Tobacco smoking is a risk factor for gastrointestinal disorders, causing mucosal damage and impairing immune responses. However, smoking has been found to be protective against ulcerative colitis (UC). Human leukocyte antigen (HLA) is a major susceptibility locus for UC, and HLA-DRB1*15:02 has the strongest effect in Asians. This study investigated the effects of smoking on the association between HLA and UC. METHODS: The study enrolled 882 patients with UC, including 526 never, 151 current, and 205 former smokers, and 3091 healthy controls, including 2124 never, 502 current, and 465 former smokers. Smoking-stratified analyses of HLA data were performed using a case-control approach. RESULTS: In a case-control approach, HLA-DRB1*15:02 was associated with UC in never smokers (ORnever smokers  = 3.20, Pnever smokers  = 7.88 × 10-23 ) but not in current or former smokers (Pcurrent smokers  = 0.72 and Pformer smokers  = 0.33, respectively). In current smokers, HLA-DQB1*06 was associated with UC (ORcurrent smokers  = 2.59, Pcurrent smokers  = 6.39 × 10-12 ). No variants reached genome-wide significance in former smokers. CONCLUSIONS: An association between UC and HLA-DRB1*15:02 was limited to never smokers. Our findings highlight that tobacco smoking modifies the effects of HLA on the risk of UC.

Association of TRAP1 with infliximab-induced mucosal healing in Crohn's disease.

BACKGROUND AND AIM: Anti-tumor necrosis factor (TNF) agents, such as infliximab (IFX), have been increasingly used to induce and maintain disease remission in patients with Crohn's disease (CD). Despite a considerable non-response rate, little is known about the genetic predictors of response to anti-TNF therapy in CD. Our aim in this study was to investigate the genetic factors associated with response to anti-TNF therapy in patients with CD. METHODS: We performed a two-stage genome-wide association study (GWAS) to identify loci influencing the response to IFX among Korean patients with CD, comprising 42 good responders with mucosal healing and 70 non-responders. The achievement of mucosal healing was assessed by endoscopy and imaging. The functional significance of TRAP1 (TNF receptor associated protein 1) was examined using dextran sodium sulfate-induced colitis model in TRAP1 transgenic mice. RESULTS: The GWAS identified rs2158962, an intronic single nucleotide polymorphism (SNP) of TRAP1, significantly associated with mucosal healing (odds ratio = 4.94; Pcombined  = 1.35 × 10-7 ). In the dextran sodium sulfate-induced acute colitis, TRAP1 transgenic mice showed a better response to IFX than the wild-type mice. CONCLUSIONS: The TRAP1 gene is associated with mucosal healing in CD patients following IFX therapy. Identifying the genetic predictors of mucosal healing to anti-TNF therapy can prevent patients from exposure to ineffective therapies.

Immunochip Meta-Analysis of Inflammatory Bowel Disease Identifies Three Novel Loci and Four Novel Associations in Previously Reported Loci.

BACKGROUND AND AIMS: Recent meta-analysis of genome-wide association studies have identified over 241 inflammatory bowel disease susceptibility loci. However, the known variants only account for a fraction of inflammatory bowel disease heritability. To identify additional susceptibility loci, we performed a trans-ethnic meta-analysis as well as an Asian-specific meta-analysis, using all published Immunochip association results of inflammatory bowel disease. METHODS: An inverse-variance fixed-effects meta-analysis was carried out across Korean and East Asian Immunochip datasets of 4156 cases and 4904 controls [Asian ancestry]. A trans-ethnic meta-analysis of inflammatory bowel disease was performed together with the European datasets of 38 155 cases and 48 485 controls genotyped on the immunochip using a Bayesian approach, Meta-Analysis of Trans-ethnic Association studies [MANTRA]. RESULTS: We identified seven novel associations, including three novel susceptibility loci at MYO10-BASP1, PPP2R3C/KIAA0391/PSMA6/NFKB1A and LRRK1 as well as four novel secondary associations within previously known loci at NCF4, TSPAN32, CIITA and VANGL2. The new loci further implicate alterations in B cell biology in Crohn's disease pathogenesis. The effects of five loci were universal across European and Asian ancestries, whereas the NCF4 and CIITA loci showed significant heterogeneity between European and East Asian populations. In addition, 103 previously known IBD loci showed supporting evidence of association with nominal significance [p < 0.05] in Asians. CONCLUSIONS: Our findings of new loci not previously associated with IBD support the importance of studying inflammatory bowel disease genetics in diverse populations.

Association of CDKN2A/CDKN2B with inflammatory bowel disease in Koreans.

BACKGROUND AND AIM: CDKN2A/CDKN2B locus on 9p21 is reported to be associated with various diseases, including cancer and cardiovascular and inflammatory diseases. Significant downregulation of CDKN2B-AS1 in inflamed colon tissue of inflammatory bowel disease (IBD) cases was reported in Europeans. This study aimed to confirm the suggestive association of CDKN2A/CDKN2B with IBD identified in our recent genome-wide association study (GWAS). METHODS: We examined the association of CDKN2A/CDKN2B locus with IBD in an additional sample of 574 IBD cases and 542 controls, totaling 4068 cases and 8074 controls. In silico study was performed at various levels for functional annotation of the causal variant. Co-localization of the GWAS association signals and the corresponding expression quantitative trait loci in IBD-related tissues was evaluated using eCAVIAR. RESULTS: An expanded GWAS showed genome-wide significant association of rs3731257 at 9p21 with IBD (odds ratio = 1.17, 95% confidence interval = 1.12-1.22, Pcombined  = 5.68 × 10-9 ) and Crohn's disease (odds ratio = 1.22, 95% confidence interval = 1.15-1.28, Pcombined  = 8.85 × 10-9 ) in the Korean population. Co-localization study suggested that both CDKN2B-AS1 and CDKN2A might be functionally associated with the locus in the small intestine. CONCLUSIONS: rs3731257 in CDKN2A/CDKN2B is an IBD-susceptible locus in Koreans, with a suggestive role for small intestine-specific gene regulation. Our findings suggested that alterations of the CDKN2A/CDKN2B locus could affect the pathophysiology of IBD.

X Chromosome-wide Association Study Identifies a Susceptibility Locus for Inflammatory Bowel Disease in Koreans.

BACKGROUND AND AIMS: Genome-wide association studies of inflammatory bowel disease identified > 200 susceptibility loci only in autosomes. This study aimed to identify inflammatory bowel disease susceptibility loci on the X chromosome. METHODS: We performed an X chromosome-wide association study in Korean patients with inflammatory bowel disease. We analysed X chromosome data from our recent genome-wide association studies, including 1505 cases [922 Crohn's disease and 583 ulcerative colitis] and 4041 controls during the discovery phase, followed by replication in additional 1989 cases [993 Crohn's disease, 996 ulcerative colitis] and 3491 controls. Sex-related differential effects of single nucleotide polymorphisms on disease were also evaluated. RESULTS: We confirmed a significant association of a previously reported inflammatory bowel disease susceptibility locus at chromosome Xq26.3 [CD40LG-ARHGEF6; odds ratio, 1.22; 95% confidence interval, 1.16-1.28; combined p = 3.79 × 10-15]. This locus accounted for 0.18% and 0.12% of genetic variance in Crohn's disease and ulcerative colitis, respectively, and increased the total autosomal chromosome genetic variance from 6.65% to 6.83% and from 5.47% to 5.59% for Crohn's disease and ulcerative colitis risk, respectively, in the Korean population. Sex-stratified analyses did not reveal sex-related differences in effect sizes. CONCLUSIONS: We confirmed the association of rs2427870 at the CD40LG-ARHGEF6 locus with an inflammatory bowel disease through an X chromosome-wide association study in a Korean population. Our data suggest that the CD40LG-ARHGEF6 locus on the X chromosome might play a role in inflammatory bowel disease pathogenesis in the Korean population.

Fine-mapping analysis revealed complex pleiotropic effect and tissue-specific regulatory mechanism of TNFSF15 in primary biliary cholangitis, Crohn's disease and leprosy.

Genetic polymorphism within the 9q32 locus is linked with increased risk of several diseases, including Crohn's disease (CD), primary biliary cholangitis (PBC) and leprosy. The most likely disease-causing gene within 9q32 is TNFSF15, which encodes the pro-inflammatory cytokine TNF super-family member 15, but it was unknown whether these disparate diseases were associated with the same genetic variance in 9q32, and how variance within this locus might contribute to pathology. Using genetic data from published studies on CD, PBC and leprosy we revealed that bearing a T allele at rs6478108/rs6478109 (r(2) = 1) or rs4979462 was significantly associated with increased risk of CD and decreased risk of leprosy, while the T allele at rs4979462 was associated with significantly increased risk of PBC. In vitro analyses showed that the rs6478109 genotype significantly affected TNFSF15 expression in cells from whole blood of controls, while functional annotation using publicly-available data revealed the broad cell type/tissue-specific regulatory potential of variance at rs6478109 or rs4979462. In summary, we provide evidence that variance within TNFSF15 has the potential to affect cytokine expression across a range of tissues and thereby contribute to protection from infectious diseases such as leprosy, while increasing the risk of immune-mediated diseases including CD and PBC.

Identification of Loci at 1q21 and 16q23 That Affect Susceptibility to Inflammatory Bowel Disease in Koreans.

Recent genome-wide association studies have identified more than 200 regions that affect susceptibility to inflammatory bowel disease (IBD). However, identified common variants account for only a fraction of IBD heritability and largely have been identified in populations of European ancestry. We performed a genome-wide association study of susceptibility loci in Korean individuals, comprising a total of 1505 IBD patients and 4041 controls. We identified 2 new susceptibility loci for IBD at genome-wide significance: rs3766920 near PYGO2-SHC1 at 1q21 and rs16953946 in CDYL2 at 16q23. In addition, we confirmed associations, in Koreans, with 28 established IBD loci (P < 2.16 × 10-4). Our findings support the complementary value of genetic studies in different populations.

Influences of XDH genotype by gene-gene interactions with SUCLA2 for thiopurine-induced leukopenia in Korean patients with Crohn's disease.

BACKGROUND: The impact of genetic variation in the thiopurine S-methyltransferase (TPMT) gene on thiopurine-induced leukopenia has been well demonstrated. Although xanthine dehydrogenase (XDH) is the second major contributor to azathioprine breakdown, polymorphisms in XDH have rarely been studied in IBD patients. We aim to access association between XDH variants and thiopurine-induced leukopenia by gene-gene interaction in a Crohn's disease (CD) population. STUDY: A total of 964 CD patients treated with thiopurines were recruited from a tertiary referral center. The association between four XDH variants (p.Gly172Arg, p.Asn1109Thr, p.Arg149Cys, and p.Thr910Lys) and thiopurine-induced leukopenia was analyzed in cases with early leukopenia (n = 66), late leukopenia (n = 264), and in controls without leukopenia (n = 632). Three non-synonymous SNPs, which we previously reported association with thiopurine-induced leukopenia, NUDT15 (p.Arg139Cys), SUCLA2 (p.Ser199Thr), and TPMT *3C were selected for epistasis analysis with the XDH variants. RESULTS: There was no significant association for two variants of XDH and thiopurine-induced leukopenia. In the epistasis analysis, only XDH (p.Asn1109Thr) * SUCLA2 (p.Ser199Thr) showed a statistically significant association with early leukopenia [odds ratio (OR) = 0.16; p = 0.03]. After genotype stratification, a positive association on the background of SUCLA2 wild-type (199Ser) between the XDH (p.Asn1109Thr) and early leukopenia (OR = 4.39; p = 0.01) was detected. CONCLUSION: Genes associated with thiopurine-induced leukopenia can act in a complex interactive manner. Further studies are warranted to explore the mechanisms underlying the effects of the combination of XDH (p.Asn1109Thr) and SUCLA2 (199Ser) on thiopurine-induced leukopenia.

Genome-wide association study of gastric adenocarcinoma in Asia: a comparison of associations between cardia and non-cardia tumours.

OBJECTIVE: Genome-wide association studies (GWAS) of gastric cancer have reported differences in single-nucleotide polymorphism (SNP) associations for tumour subtypes, particularly when divided by location into the gastric cardia versus the non-cardia. DESIGN: Here we present results for a GWAS using 2350 East Asian gastric cancer cases divided as 1189 gastric cardia and 1027 gastric non-cardia cases and 2708 controls. We also included up to 3042 cardia cases, 4359 non-cardia cases and 7548 controls for replication from two Chinese studies and one Korean study. From the GWAS, we selected 12 top SNPs for each gastric cancer subtype, 4 top SNPs for total gastric cancer and 1 SNP in MUC1 for replication testing. RESULTS: We observed genome-wide significant associations for rs10074991 in PRKAA1 at 5p13.1 for cardia (p=7.36×10(-12)) and non-cardia cancers (p=2.42×10(-23)) with per allele OR (95% CI) for the combined endpoint of 0.80 (0.77 to 0.83). At 6p21.1, rs2294693 near UNC5CL was significantly associated with gastric non-cardia cancer risk (p=2.50×10(-8)), with OR (95% CI) of 1.18 (1.12 to 1.26), but there was only a nominal association for cardia cancer (p=1.47×10(-2)). We also confirmed a previously reported association for rs4072037 in MUC1 with p=6.59×10(-8) for total gastric cancer and similar estimates for cardia and non-cardia cancers. Three SNPs in PSCA previously reported to be associated with gastric non-cardia cancer showed no apparent association for cardia cancer. CONCLUSIONS: Our results suggest that associations for SNPs with gastric cancer show some different results by tumour location in the stomach.

Immunochip analysis identification of 6 additional susceptibility loci for Crohn's disease in Koreans.

BACKGROUND: Crohn's 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, odds ratio [OR] = 1.45), ZNF365 at 10q21 (rs224143; P = 2.20 × 10, OR = 1.38), ZMIZ1 at 10q22 (rs1250569; P = 3.05 × 10, OR = 1.30), NKX2-3 at 10q24 (rs4409764; P = 7.93 × 10, OR = 1.32), PTPN2 at 18p11 (rs514000; P = 9.00 × 10, OR = 1.33), and USP25 at 21q11 (rs2823256; P = 2.49 × 10, 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.

A common missense variant in NUDT15 confers susceptibility to thiopurine-induced leukopenia.

Thiopurine therapy, commonly used in autoimmune conditions, can be complicated by life-threatening leukopenia. This leukopenia is associated with genetic variation in TPMT (encoding thiopurine S-methyltransferase). Despite a lower frequency of TPMT mutations in Asians, the incidence of thiopurine-induced leukopenia is higher in Asians than in individuals of European descent. Here we performed an Immunochip-based 2-stage association study in 978 Korean subjects with Crohn's disease treated with thiopurines. We identified a nonsynonymous SNP in NUDT15 (encoding p.Arg139Cys) that was strongly associated with thiopurine-induced early leukopenia (odds ratio (OR) = 35.6; P(combined) = 4.88 × 10(-94)). In Koreans, this variant demonstrated sensitivity and specificity of 89.4% and 93.2%, respectively, for thiopurine-induced early leukopenia (in comparison to 12.1% and 97.6% for TPMT variants). Although rare, this SNP was also strongly associated with thiopurine-induced leukopenia in subjects with inflammatory bowel disease of European descent (OR = 9.50; P = 4.64 × 10(-4)). Thus, NUDT15 is a pharmacogenetic determinant for thiopurine-induced leukopenia in diverse populations.

TNFSF15 is an independent predictor for the development of Crohn's disease-related complications in Koreans.

BACKGROUND: Crohn's disease (CD) is a chronic idiopathic inflammatory bowel disease involving the whole gastrointestinal tract. TNFSF15 has been proved as a susceptibility gene for CD, but there are few reports about the association between TNFSF15 single nucleotide polymorphisms (SNPs) and the clinical course of CD. AIM: To investigate the association between TNFSF15 genotypes and the clinical course of CD in Koreans. METHODS: A total of 906 CD patients having TNFSF15 genotype data and clinical information were recruited from CD registry database of a tertiary referral center. The association between five TNFSF15 SNPs (rs4574921, rs3810936, rs6478108, rs6478109, and rs7848647) and various clinical parameters including stricture, non-perianal penetrating complications, bowel resection, and reoperation was investigated. RESULTS: Among the five SNPs, rs6478108 CC genotype was associated with the development of stricture and non-perianal penetrating complications during follow-up (HR for stricture=1.706, 95% confidence interval 1.178-2.471, P=0.005; HR for non-perianal penetrating complications=1.667, 95% confidence interval 1.127-2.466, P=0.010), and rs4574921 CC genotype was associated with the development of perianal fistula (HR=2.386, 95% confidence interval 1.204-4.727, P=0.013) by multivariate analysis. However, there was no significant association of cumulative operation and reoperation rate with 5 SNPs of TNFSF15. CONCLUSION: In Korean patients with CD, non-risk allele homozygotes of TNFSF15 SNPs rs6478108 and rs4574921 are independent genetic predictive factors for the development of strictures/non-perianal penetrating complications and perianal fistula, respectively.

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: Crohn's 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.

Association of FCGR2A, JAK2 or HNF4A variants with ulcerative colitis in Koreans.

BACKGROUND: Recent genome-wide association studies have identified over 40 candidate genes contributing to ulcerative colitis susceptibility. The goal of this study was to test the reported ulcerative colitis susceptibility genes including FCGR2A, SLC26A3, JAK2 and HNF4A in Korean patients with ulcerative colitis and Crohn's disease. METHODS: Five single nucleotide polymorphisms from 4 loci including FCGR2A, SLC26A3, JAK2 and HNF4A were genotyped in 661 patients with ulcerative colitis, 642 patients with Crohn's disease and 601 healthy controls. RESULTS: Statistically significant associations with ulcerative colitis were found at FCGR2A (rs1801274, p=2.3×10(-4), OR=0.70 (95% CI=0.57-0.84) under the allelic model), the JAK2 locus (rs10975003, p=6.7×10(-4), OR=1.43 (95% CI=1.16-1.77) under the allelic model) and HNF4A (rs6017342, p=0.002, OR=0.66 (95% CI=0.51-0.85) under the allelic model). The association of FCGR2A was much stronger in female patients with ulcerative colitis (p=5.7×10(-6)) than in males (p=0.50). Except rs10975003 from the JAK2 locus, none showed positive association with Crohn's disease. CONCLUSIONS: Our data suggest that FCGR2A, JAK2 or HNF4A variants play a role in the pathogenesis of ulcerative colitis in Koreans.

Association of CARD8 with inflammatory bowel disease in Koreans.

Caspase recruitment domain (CARD)-containing protein 8 (CARD8) is a potential candidate risk gene for inflammatory bowel disease (IBD) because of its role as a component of the NALP3 inflammasome and as an inhibitor of nuclear factor-kappa B. Previous studies examining the association of a CARD8 single-nucleotide polymorphism (SNP) (rs2043211, p.Cys10X) with IBD yielded mixed results in Caucasians that may result from interaction with NALP3 or NOD2 (nucleotide-binding oligomerization domain 2) variants. To understand the genetic association between CARD8/NALP3 and IBD in Koreans, we investigated seven CARD8, four NALP3 and four NOD2 SNPs in 650 Crohn's disease (CD), 660 ulcerative colitis (UC) patients and 688 controls from the Korean population. rs2043211 of CARD8 showed significant association with UC (P = 0.011; odds ratio = 1.50, 95% confidence intervals = 1.12-2.00, P = 0.006 under recessive model). In contrast, an SNP in intron 1, rs1972619, was associated with CD only (P = 0.033). None of the NALP3 or NOD2 SNPs was significantly associated with CD or UC in the Korean populations. The stop allele of rs2043211 was associated with higher serum interleukin-1ß levels only in female patients with UC (P = 0.027). Our data suggest that CARD8 variants might have roles in the pathogenesis of CD and UC in Koreans.

No association between TNFSF15 and IL23R with ulcerative colitis in Koreans.

Recent genome-wide association studies have shown that some Crohn's disease (CD)-associated loci also contribute to ulcerative colitis (UC) susceptibility. To understand the genetic relationship between the two forms of inflammatory bowel disease, we investigated the well-established CD-susceptibility genes TNFSF15 (tumor necrosis factor ligand superfamily, member 15) and IL23R in Korean patients with UC. Eight TNFSF15 and five IL23R single-nucleotide polymorphisms were genotyped in 654 patients with UC and in 601 healthy controls. There was no association between TNFSF15 or IL23R variants and UC in Korean individuals, in contrast to previous reports of a shared association of the IL23R gene with both CD and UC in Caucasian individuals. Our data suggest that neither TNFSF15 nor IL23R variants contribute to UC susceptibility in Koreans.