Child ; Crohn Disease ; genetics ; Female ; Humans ; Infant ; Male

OBJECTIVETo assess the associations of death receptor DR4 and DR5 gene polymorphisms with Crohn's disease (CD).

METHODSA total of 295 CD patients and 490 healthy controls were recruited. Three single nucleotide polymorphisms (SNPs) of the DR4 (rs13278062, rs20575) and DR5 (rs1047266) genes were determined with a SNaPshot method. Unconditional logistic regression analysis was carried out for determining the allelic and genotypic differences of the three SNPs between CD patients and the controls, as well as the influence of the DR4 and DR5 gene polymorphisms on the clinical features of CD patients. Linkage disequilibrium and haplotype analysis were calculated by haplotype 4.2 and R language software. A gene-gene interaction model was established to analyze whether the three SNPs can exert a synergistic effect on the susceptibility to CD.

RESULTSThe mutant allele (T) and genotype (GT+TT) of DR4 (rs13278062) were increased among CD patients compared to the controls (37.12% vs. 32.04%, P = 0.040, 95%CI: 1.010-1.550; 62.71% vs. 54.90%, P = 0.032, 95%CI: 1.028-1.855, respectively). However, the allelic and genotypic frequencies of DR4 (rs20575) and DR5 (rs1047266) did not differ between the two groups (all P > 0.05). Based on the Montreal Classification Standards, the CD patients were stratified by locations and behaviors of the disease. After multiple comparison correction (P < 0.0125), compared to ileocolonic CD patients respectively, the mutant allele (T) and genotype (GT+TT) of the rs13278062 polymorphism were significantly increased in colonic CD patients (41.04% vs. 25.64%, P = 0.002, 95%CI: 0.315-0.778; 66.04% vs. 41.03%, P = 0.001, 95%CI: 0.196-0.655, respectively) and terminal ileum CD patients (41.44% vs. 25.64%, P = 0.002, 95%CI: 0.311-0.762; 74.77% vs. 41.03%, P < 0.001, 95%CI: 0.126-0.437, respectively). In comparison to penetrating CD patients, the mutant allele (T) and genotype (GT+TT) of DR4 (rs13278062) were significantly decreased in stricturing CD patients (32.29% vs. 48.91%, P = 0.007, 95%CI: 0.300-0.828; 57.29% vs. 86.96%, P = 0.001, 95%CI: 0.078-0.520, respectively). A similar conclusion was drawn for the mutant genotype (GT+TT) of DR4 (rs13278062) in non-stricturing, non-penetrating CD patients (58.82% vs. 86.96%, P = 0.001, 95%CI: 0.086-0.536). Haplotype analysis indicated that the CT haplotype formed by rs20575 and rs13278062 was increased in CD patients compared to the controls (37.1% vs. 31.8%, P = 0.029, OR=1.279, 95%CI: 1.022-1.600). The outcome of a gene-gene interaction model indicated that the mutant genotype (GT+TT) of DR4 (rs13278062) and mutant genotype (CT+TT) of DR5 (rs1047266) may play a negatively synergistic role in CD patients (B = - 0.483, OR = 0.617, P = 0.030).

CONCLUSIONThe rs13278062 polymorphism of the DR4 gene not only can confer an increased risk for CD, but may also influence the location of the lesions and the disease behaviors. The CT haplotype formed by rs20575 and rs13278062 may be an independent risk factor for CD. Furthermore, the mutant genotype (GT+TT) of DR4 (rs13278062) and mutant genotype (CT+TT) of DR5 (rs1047266) may exert a negative synergistic effect on CD.

Adult ; Crohn Disease ; genetics ; Epistasis, Genetic ; Female ; Genetic Predisposition to Disease ; Genotype ; Haplotypes ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; genetics

OBJECTIVETo understand the relationship between the susceptibility to inflammatory bowel disease (IBD) and ATG16L1 gene single nucleotide polymorphism (SNP) site, rs2241880.

METHODSPeripheral blood samples were collected from 80 IBD patients (including 40 with Crohn's disease and 40 with ulcerative colitis) and 50 healthy controls, and the genomic DNA was extracted from the white blood cells. Specific primers were designed according to the target gene sequence for PCR amplification of the target gene fragment, and the PCR products were purified followed by sequence analysis of the target region of ATG16L1 gene. The results of the sequence analysis were compared with the BenBank data to analyze the relationship between the allele gene polymorphisms and the susceptibility to Crohn's disease.

RESULTSNo significant differences were noted in the ATG16L1 gene SNP site rs2241880 polymorphisms among the patients with Crohn's disease, ulcerative colitis and the control subjects (Chi(2)=4.94, P=0.293).

CONCLUSIONATG16L1 gene polymorphisms in the SNP site rs2241880 are not found to correlate to the susceptibility to Crohn's disease as reported in literature. The SNP site associated with Crohn's disease susceptibility identified in foreign populations does not seem to be identical with that in Chinese population.

Adult ; Autophagy ; genetics ; Autophagy-Related Proteins ; Base Sequence ; Carrier Proteins ; genetics ; Colitis, Ulcerative ; genetics ; Crohn Disease ; genetics ; Female ; Genetic Predisposition to Disease ; genetics ; Humans ; Inflammatory Bowel Diseases ; genetics ; Male ; Middle Aged ; Phagosomes ; genetics ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA

BACKGROUND/AIMS: Several studies from Western populations have recently shown that three mutations in NOD2 gene (C2104T, G2722C, and 3020insC) are associated with susceptibility to Crohn's disease (CD). However, three mutations were shown not to be associated with CD in Japanese and Chinese population. Here, we have analyzed the frequency of three NOD2 mutations in Korean patients to determine whether the NOD2 mutations are associated with susceptibility to CD in Korean population. METHODS: Blood samples were obtained from 128 patients with CD, 47 patients with ulcerative colitis, 19 Behcet's colitis, and 200 healthy controls. DNA in the region of three NOD2 mutations was sequenced by single base extension method, and the frequency of mutations were analyzed. RESULTS: Among the subjects in our study groups, including patients with CD, ulcerative colitis, Behcet's colitis, and healthy controls, none had NOD2 mutations. CONCLUSIONS: Our results indicate that although three NOD2 mutations are associated with susceptibility to CD in Western populations, these might be rare and may not be associated with susceptibility to CD in Korean patients.
Adolescent ; Adult ; Aged ; Child ; Crohn Disease/*genetics ; English Abstract ; Female ; Genotype ; Humans ; Intracellular Signaling Peptides and Proteins/*genetics ; Korea ; Male ; Middle Aged ; *Mutation ; Polymorphism, Single Nucleotide

OBJECTIVETo investigate the association between TaqI, BsmI, and ApaI polymorphisms of vitamin D receptor (VDR) gene and pediatric Crohn's disease (CD) in China.

METHODSNineteen children with CD were selected as a case group, and 122 healthy children who underwent physical examination were selected as a control group. Serum 25-hydroxyvitamin D3 [25(OH)D3] levels were measured using ELISA. The TaqI, BsmI, and ApaI polymorphisms of VDR gene were determined by gene sequencing, and the two groups were compared in terms of genotype and allele frequencies.

RESULTSThe case group had significantly lower serum 25(OH)D3 levels than the control group (17.3±2.4 ng/mL vs 26.9±2.1 ng/mL; P<0.05). There were no significant differences in the frequencies of genotypes and alleles of TaqI, BsmI, and ApaI polymorphisms between the case and control groups (P>0.05).

CONCLUSIONSChildren with CD have low serum 25(OH)D3 levels. TaqI, BsmI, and ApaI polymorphisms of VDR gene may not be associated with susceptibility to CD among the Chinese population.

Adolescent ; Calcifediol ; blood ; Child ; Child, Preschool ; Crohn Disease ; blood ; genetics ; Female ; Humans ; Male ; Polymorphism, Single Nucleotide ; Receptors, Calcitriol ; genetics ; Sequence Analysis, DNA

OBJECTIVETo observe the effects of Huangqi Jiegeng Decoction (HJD) and Huangqi Huanglian Decoction (HHD) on the intercellular adhesion molecule-I (ICAM-1) content in the lung and colon of rats with Crohn's disease (CD).

METHODSTotally 56 rats were used to establish the CD rat model using TNBS water solution/absolute alcohol enema (with the model successful rate of 63.0%). Seven rats randomly selected from 35 successfully modeled rats and from the normal group were recruited as the model group and the normal group before intervention. The rest 28 successfully modeled rats were randomly divided into the model group, the Western medicine group (treated with salazosulfapyridine at 0.4 g/kg), the HJD group (20.5 g/kg), and the HHD group (20.8 g/kg), 7 in each group. Another 7 normal rats were recruited as the normal group. Equal volume of pure water was given to rats in the normal group and the model group by gastrogavage, twice daily, for 3 successive weeks. The protein and mRNA expressions of ICAM-1 in the lung and colon tissues were determined before and after intervention using Western blot and RT-PCR.

RESULTSCompared with the normal control group, the protein and mRNA levels of ICAM-1 in the colon tissue, and the mRNA level of ICAM-1 in the lung tissue increased (P< 0.01, P<0.05). After intervention the protein and mRNA levels of ICAM-1 in the colon tissue and the lung tissue increased (P<0.01) in the model group. Compared with the model group at the same time point, the protein and mRNA levels of ICAM-1 in the colon tissue and the lung tissue decreased in each medication group after intervention (P<0.01, P<0.05). Compared with the Western medicine group, the protein level of ICAM-1 in the lung tissue decreased more significantly in the HJD group (P<0.05). The protein level of ICAM-1 in the colon tissue also decreased in the HHD group (P<0.05).

CONCLUSIONSHHD and HJD both could down-regulate the over-expressed ICAM-1 in the lung and colon tissues of CD rats. HHD was prominent in inhibiting the adherence of colonic inflammatory cells and attenuating local immunopathological injury. HJD was prominent in attenuating inflammation and injury in the lung, and preventing pulmonary fibrosis.

Animals ; Colon ; metabolism ; Crohn Disease ; metabolism ; pathology ; Drugs, Chinese Herbal ; pharmacology ; Intercellular Adhesion Molecule-1 ; genetics ; metabolism ; Lung ; metabolism ; Male ; RNA, Messenger ; genetics ; Rats ; Rats, Wistar

BACKGROUND/AIMS: Toll-like receptors (TLRs) serve as pattern recognition receptors that recognize specific molecular patterns of pathogens and can mediate the production of proinflammatory cytokines. Recently, TLRs have been identified as susceptibility genes for Crohn's disease (CD) in several studies from Western populations. We investigated the association of genetic variations in TLR4 and TLR9 with CD in Korean population. METHODS: In 380 CD cases and 380 healthy controls, we performed genotyping for TLR4 Asp299Gly (rs4986790) and Thr399Ile (rs4986791). The genetic variations in the TLR9 -1237T/C (rs5743836) were also examined. RESULTS: Among CD patients genotyped for TLR4 Asp299Gly and TLR9 -1237T/C, none had variant alleles. Similarly, none of the subjects genotyped for TLR4 Thr399Ile showed genetic variations. CONCLUSIONS: Our results indicate that the major genetic variations in TLR4 and TLR9 are rare and may not be associated with susceptibility to CD in Koreans.
Adolescent ; Adult ; Alleles ; Asian Continental Ancestry Group/*genetics ; Crohn Disease/diagnosis/ethnology/*genetics ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Republic of Korea ; Toll-Like Receptor 4/*genetics ; Toll-Like Receptor 9/*genetics

BACKGROUND/AIMS: Although the importance of genetic susceptibility to inflammatory bowel disease (IBD) has been established by epidemiological studies, the genes involved remain poorly understood. The aim of this study was to assess the role of single nucleotide polymorphisms of tumor necrosis factor-alpha(TNF-alpha) and interleukin-10 (IL-10) genes in genetic susceptibility of IBD. METHODS: Blood samples were obtained from 91 patients with ulcerative colitis (UC), 63 patients with Crohn's disease (CD), and 200 healthy controls (HC). DNA was extracted from blood leukocytes for IL-10 and TNF-alpha genotyping by single base extension reaction. Genotypes and allelic frequencies were compared between IBD patients and HC, and among subgroups of the patients. RESULTS: The frequency of -308A allele of TNF-alpha was significantly lower in CD patients than in HC (p=0.005). The frequency of -238A allele of TNF-alpha was significantly higher in CD patients with perianal lesion than those without perianal lesion. On the other hand, the frequency of -308A allele of TNF-alpha was significantly higher in ANCA-positive IBD patients than ANCA-negative IBD patients. There were no significant differences in allelic frequencies in the promoter region of IL-10 between IBD patients and HC. CONCLUSIONS: The TNF-alpha gene polymorphisms at positions -308 and -238 may have influences on the susceptibility to CD or the behavior of CD.
Adolescent ; Adult ; Aged ; Colitis, Ulcerative/*genetics ; Crohn Disease/*genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Interleukin-10/*genetics ; Male ; Middle Aged ; *Polymorphism, Single Nucleotide ; Tumor Necrosis Factor-alpha/*genetics

Inflammatory bowel diseases (IBD) is heterogeneous, chronic relapsing disorder. Inappropriate and exaggerated immune response for the luminal antigen is known as a main pathogenesis. Genetic, infectious, and environmental factors are responsible for unbalanced immune response, but the definite pathogenesis is still unclear. Genetic factor is the most important role of all. That is based on high concordance rate of identical twins and family history. The incident rate and prevalence of IBD for the Asian population is relatively lower than Western population, and the lack of NOD2 or TLR4 genetic polymorphisms in Korea and Japanese population suggests the difference in genetic background between Asian and Western population. In Korea, the case of familial aggregation of IBD is pretty rare. We report a case of the daughter with ulcerative colitis and her mother with Crohn's disease who have a -159C/T promoter polymorphism of CD14 gene for IBD.
Antigens, CD14/genetics ; Colitis, Ulcerative/*diagnosis/drug therapy/genetics ; Colonoscopy ; Crohn Disease/*diagnosis/genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Mesalamine/therapeutic use ; Middle Aged ; Mothers ; Polymorphism, Restriction Fragment Length ; Tomography, X-Ray ; Young Adult

Inflammatory bowel diseases (IBD) is heterogeneous, chronic relapsing disorder. Inappropriate and exaggerated immune response for the luminal antigen is known as a main pathogenesis. Genetic, infectious, and environmental factors are responsible for unbalanced immune response, but the definite pathogenesis is still unclear. Genetic factor is the most important role of all. That is based on high concordance rate of identical twins and family history. The incident rate and prevalence of IBD for the Asian population is relatively lower than Western population, and the lack of NOD2 or TLR4 genetic polymorphisms in Korea and Japanese population suggests the difference in genetic background between Asian and Western population. In Korea, the case of familial aggregation of IBD is pretty rare. We report a case of the daughter with ulcerative colitis and her mother with Crohn's disease who have a -159C/T promoter polymorphism of CD14 gene for IBD.
Antigens, CD14/genetics ; Colitis, Ulcerative/*diagnosis/drug therapy/genetics ; Colonoscopy ; Crohn Disease/*diagnosis/genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Mesalamine/therapeutic use ; Middle Aged ; Mothers ; Polymorphism, Restriction Fragment Length ; Tomography, X-Ray ; Young Adult