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Biomedical subjects

J B A Crusius

Publications and source records attributed to J B A Crusius.

At least 19 recordsLinked to original sources
PubMed2006

Description of the ICTI consortium: an integrated approach to the study of Chlamydia trachomatis infection.

The use of an integrated approach to the study of Chlamydia trachomatis infection of the female genital tract, presented at the mini-symposium "Chlamydia trachomatis infections" and described in the thesis of Joseph M. Lyons, has resulted in the creation of the ICTI consortium. The ICTI consortium is based on strong interaction and collaboration between basic scientists, clinicians, epidemiologists, and health care policy makers. This translational approach will help to further the valuable insight into the immunopathogenesis of this sexually transmitted infection (STI) and the development of new intervention strategies, including the vaccines and screening programs necessary to effectively diagnose, treat and prevent C. trachomatis infection. A background of the need for this integrated approach is presented and the goals and participants of the consortium are described.

Animals↗
PubMed2005

Combined carriership of TLR9-1237C and CD14-260T alleles enhances the risk of developing chronic relapsing pouchitis.

AIM: To investigate the single nucleotide polymorphisms (SNPs) in genes involved in bacterial recognition and the susceptibility to pouchitis or pouchitis severity. METHODS: Analyses of CD14 -260C>T, CARD15/NOD2 3020insC, Toll-like receptor (TLR)4 +896A>G, TLR9 -1237T>C, TLR9+2848G>A, and IRAKM + 22148G>A SNPs were performed in 157 ileal-pouch anal anastomosis (IPAA) patients (79 patients who did not develop pouchitis, 43 infrequent pouchitis patients, 35 chronic relapsing pouchitis patients) and 224 Italian Caucasian healthy controls. RESULTS: No significant differences were found in SNP frequencies between controls and IPAA patients. However, a significant difference in carriership frequency of the TLR9-1237C allele was found between the infrequent pouchitis and chronic relapsing pouchitis groups [P = 0.028, oddos ratio (OR) = 3.2, 95%CI = 1.2-8.6]. This allele uniquely represented a 4-locus TLR9 haplotype comprising both studied TLR9 SNPs in Caucasians. Carrier trait analysis revealed an enhanced combined carriership of the alleles TLR9 -1237C and CD14 -260T in the chronic relapsing pouchitis and infrequent pouchitis group (P = 0.018, OR = 4.1, 95%CI = 1.4 -12.3). CONCLUSION: There is no evidence that the SNPs predispose to the need for IPAA surgery. The significant increase of the combined carriership of the CD14 -260T and TLR9 -1237C alleles in the chronic relapsing pouchitis group suggests that these markers identify a subgroup of IPAA patients with a risk of developing chronic or refractory pouchitis.

Adult↗
PubMed2005

The IL-1 gene family and bone involvement in celiac disease.

Celiac disease (CD) is associated with decreased bone mineral mass. Its pathogenesis is multifactorial since both systemic and local mechanisms may play a role. Our objective was to determine whether single-nucleotide polymorphisms in genes encoding members of the interleukin-1 family are associated with bone damage measured by densitometry in a series of 71 adult CD patients assessed at diagnosis. When compared with non-carrier CD patients, carriers of allele T of the interleukin-1beta gene (IL1B-511T) had a significantly lower bone mass at the total skeleton level (p = 0.0484) and a greater prevalence of osteopenia/osteoporosis (p = 0.0102). To our knowledge, this is the first evidence on the association between a genetic predisposition and low bone mass in CD patients. This finding supports the postulated inflammation-associated bone loss pathogenesis as one of the causes of bone weakness in CD.

Adult↗
PubMed2005

A functional interleukin-10 mutation in Dutch patients with Crohn's disease.

BACKGROUND AND AIMS: Interleukin-10 is an anti-inflammatory and immunomodulatory cytokine. Interleukin-10 deficient mice are prone to develop chronic colitis. Administration of recombinant human interleukin-10 has been proposed to have a beneficial effect in a subgroup of patients with Crohn's disease. Recently, we found an interleukin-10 Gly15Arg mutation in a family with Crohn's disease which is associated with reduced interleukin-10 secretion by in vitro stimulated monocytes and lymphocytes. We hypothesised that this interleukin-10 mutation plays a role in maintaining the inflammatory process in Crohn's disease in some families. PATIENTS AND METHODS: We evaluated interleukin-10 Gly15Arg in 379 patients with Crohn's disease, and 75 unrelated healthy controls. Also, first degree family members of interleukin-10 Gly15Arg carriers were evaluated. Additionally, mutation carriers and their relatives were evaluated for CARD15 R702W, G908R, and 1007fs. RESULTS: Two patients with Crohn's disease were heterozygous for the interleukin-10 Gly15Arg mutation. No homozygotes were found. The Gly15Arg mutation was not observed in the controls. In first degree family members of the Crohn's disease-affected interleukin-10 Gly15Arg carriers, the mutation was found in Crohn's disease-affected as well as in their apparently healthy individuals. All family members carried one or two CARD15 mutation(s). CONCLUSION: The interleukin-10 Gly15Arg mutation is rare in patients with Crohn's disease, and is not associated with the disease in the Netherlands.

Adolescent↗
PubMed2005

No allelic variant associations of the IL-1 and TNF gene polymorphisms in the susceptibility to duodenal ulcer disease.

Recent studies have reported the association of a pro-inflammatory profile of genetic polymorphisms in IL-1B, IL-1RN, TNF-A, and IL-10 genes with an increased risk of non-cardia gastric cancer. Because gastric cancer and duodenal ulcer are mutually exclusive outcomes of Helicobacter pylori infection, we aimed to investigate possible allelic variant associations of several functional polymorphisms in the IL-1B, IL-1RN, TNFA, and LTA genes in the susceptibility to duodenal ulcer. Genomic DNA from 118 patients with duodenal ulcer and 97 healthy controls was typed for the IL-1B polymorphisms at positions -511, -31, and +3954, the VNTR polymorphism in intron 2 of the IL-1RN gene, the TNFA-308, TNFA -238, and the NcoI and BsI LTA polymorphisms by PCR, SSCP and TaqMan assays. H. pylori infection and non-steroidal anti-inflammatory drugs (NSAIDs) use was investigated in patients and controls. Logistic regression analysis identified H. pylori infection (OR: 12.86; 95%CI: 3.85-43), NSAID use (OR: 11.95; 95%CI: 4.19-34.05), and family history-ulcer (OR: 3.79; 95%CI: 1.68-8.54) as independent risk factors for duodenal ulcer. When the effect of the combinations of IL-1 and TNF genotypes was studied we found that the distribution of all possible combinations of these eight polymorphisms was similar in duodenal ulcer patients and controls. The simultaneous carriage of alleles IL-1RN*2/IL-1B -31T/IL-1B -511C/IL-IB +3954C/TNF-HaplotypeE negative (termed in some studies as 'low-producing' alleles) was increased in H. pylori-positive duodenal ulcer patients compared to H. pylori-infected healthy controls (10.5% vs. 5.9%) although the difference did not reach statistical significance (OR: 1.85; 95%CI: 0.57-5.99, P = 0.41). Moreover, no differences were found with respect to H. pylori status, NSAID use, age, gender, smoking habit, type of complication, recurrence of the ulcer, and need for surgical treatment. Our data show no association between allelic variants of IL-1 and TNF gene polymorphisms in the susceptibility to and final outcome of duodenal ulcer.

Alleles↗
PubMed2005

No evidence for involvement of the Toll-like receptor 4 (TLR4) A896G and CD14-C260T polymorphisms in susceptibility to ankylosing spondylitis.

OBJECTIVES: Ankylosing spondylitis (AS) is a multifactorial and polygenic disease. Apart from HLA, other genes very probably play a role in disease susceptibility. Indigenous bacteria of the gastrointestinal flora appear to play a role in the pathogenesis of the disease; therefore, genes controling the innate and acquired immune response are good candidates to study disease susceptibility. CD14 and Toll-like receptor 4 (TLR4) are key receptors for the sensing of bacteria. The CD14 C-260T and TLR4 A896G single nucleotide polymorphims are associated with aberrant signal transduction for bacterial agonists. METHODS: The distribution of the CD14 C-260T and TLR4 A896G polymorphisms was studied in genomic DNA from 113 unrelated white Dutch AS patients and 170 ethnically matched healthy controls. The diagnosis of AS was made according to the modified New York criteria. The CD14 C-260T and TLR4 A896G polymorphisms were genotyped by PCR-RFLP methods. RESULTS: No significant differences were found between patients and controls in the frequencies of the carriership of the less frequent CD14-260T allele (odds ratio 0.65; 95% confidence interval 0.37 to 1.15) or the TLR4 896G allele (1.68; 0.67 to 4.19). CONCLUSIONS: There is no evidence for involvement of the CD14 C-260T or TLR4 A896G polymorphisms in susceptibility to AS. An important role of bacteria and genetic predisposition of the innate immune system in cases of AS cannot be excluded by these findings. Therefore, studies of the surprisingly highly polymorphic candidate genes in this field should be continued.

Adult↗
PubMed2005

Susceptibility to ankylosing spondylitis: no evidence for the involvement of transforming growth factor beta 1 (TGFB1) gene polymorphisms.

BACKGROUND: Genetic factors are thought to be crucial in the pathogenesis of ankylosing spondylitis. Transforming growth factor beta 1 (TGF beta 1) is a multifunctional cytokine that plays a key role in inflammation. Two functional single nucleotide polymorphisms (SNPs) in the TGFB1 gene have been described: TGFB1 T869C and TGFB1 G915C. OBJECTIVE: To determine whether these SNPs contribute to ankylosing spondylitis susceptibility or its disease characteristics. METHODS: Genomic DNA was isolated from the peripheral blood of 134 patients with ankylosing spondylitis and 194 healthy blood donors. All subjects were unrelated and of white Dutch ethnicity. The diagnosis of ankylosing spondylitis was made according to the modified New York criteria. The TGFB1 T869C and TGFB1 G915C SNPs were genotyped by a polymerase chain reaction-single strand conformation polymorphism haplotyping method. RESULTS: No significant differences were found between patients and controls in genotype, allele, and haplotype frequencies or in the carrier rate of the rare alleles of the TGFB1 T869C and TGFB1 G915C SNPs. CONCLUSIONS: TGFB1 T869C and TGFB1 G915C SNPs are not major factors in the susceptibility to ankylosing spondylitis or its disease characteristics.

Adult↗
PubMed2005

Polymorphisms of CD14 gene and TLR4 gene are not associated with ulcerative colitis in Chinese patients.

BACKGROUND AND AIMS: Toll-like receptor 4 and CD14 are the components of the lipopolysaccharide receptor complex. The aim of this study was to investigate the associations between polymorphisms TLR4 Asp299Gly and CD14 C-260T and Chinese patients with ulcerative colitis (UC). METHODS: Using a polymerase chain reaction based restriction fragment length polymorphism, the study genotyped polymorphisms TLR4 Asp299Gly and CD14 C-260T in 114 patients with UC and 160 healthy controls in the Chinese Han population. Moreover a comparison was made with 170 healthy Dutch white subjects. RESULTS: No TLR4 Asp299Gly mutation was detected in any patients or healthy controls in the Chinese Han population, which was similar to Japanese subjects, but the mutation occurred in 10% of the Dutch white subjects. There were no significant differences of CD14 genotypes between healthy controls and the patients with UC.

Asian People↗
PubMed2004

Defining the contribution of the HLA region to cis DQ2-positive coeliac disease patients.

The major genetic susceptibility to coeliac disease is contributed by the human leukocyte antigen (HLA) region. The primary association is with the HLA-DQ2 molecule, encoded by the DQA1*05 and DQB1*02 alleles, which is expressed by over 90% of patients. The aim of our study was to perform an extensive scan of the entire HLA region to determine whether there is evidence for the presence of additional HLA susceptibility genes for coeliac disease in the Dutch population, acting independently of DQ2. In all, 16 microsatellite markers and the DQA1 and DQB1 genes were genotyped in simplex cis DQ2-positive coeliac disease families and cis DQ2-positive control families. Allele frequencies of markers on phase-known DQ2-positive haplotypes transmitted to patients were compared to a combined group of DQ2-positive nontransmitted and control haplotypes, thereby controlling for the DQ2 contribution. No significant differences at any of the marker loci were detected, suggesting that DQ2 is the major HLA risk factor for coeliac disease. Individuals homozygous for DQ2 or heterozygous for DQA1*05-DQB1*02/DQA1*0201-DQB1*02 were found to be at five-fold increased risk for development of coeliac disease (P<10(-8)). This risk seems to be conferred by the presence of a second DQB1*02 allele next to one DQA1*05-DQB1*02 haplotype, independently of the second DQA1 allele.

Adolescent↗
PubMed2004

Polymorphisms in the genes encoding interferon-gamma and interferon-gamma receptors in multiple sclerosis.

Genome screens suggest that several genes, each contributing to a small extent, are involved in multiple sclerosis (MS) susceptibility. Simultaneous analysis of related genes may improve the power to detect such small effects. Interferon-gamma (IFN-gamma), mediating its effects through the IFN-gamma receptor, is a pleiotropic, pro-inflammatory cytokine for which a detrimental effect on the course of MS has been reported. The role of IFN-gamma receptor 1 (IFNGR1) and IFN-gamma receptor 2 (IFNGR2) gene polymorphisms has not been studied in MS, and, for the IFNG gene polymorphism there is only one previous study, which incorporates clinical, but not imaging, data. The aim of this study was to investigate whether polymorphisms in the IFNG and IFNGR1 and IFNGR2 genes are associated with susceptibility to MS, or disease characteristics, as defined by clinical and imaging criteria. Genotypes for IFNG, IFNGR1 and IFNGR2 were determined in 509 patients with MS and in 193 healthy controls. Patient files were reviewed for disease course, age at onset of disease, and rate of progression. Serial magnetic resonance imaging (MRI) data were available for 107 patients. No significant differences in the distribution of IFNG, IFNGR1 and IFNGR2 genotype and allele frequencies were found between patients and controls. A progressive, as opposed to a relapsing, onset was significantly more frequent in carriers of the IFNGR2 allele Arg64 (P = 0.028). Moreover, IFNGR2 allele Arg64 carriers had a lower black hole ratio than non-carriers (P = 0.016). No other associations with clinical parameters, such as age at onset or rate of progression, or with imaging parameters, were observed. The IFNG intron 1 gene polymorphism studied is unlikely to play a major role in MS susceptibility or disease course. The IFNGR1 and IFNGR2 gene polymorphisms studied do not exert an important influence on MS susceptibility, but allele IFNGR2*Arg64 may be associated with a progressive disease onset.

Adult↗
PubMed2004

A microarray screen for novel candidate genes in coeliac disease pathogenesis.

BACKGROUND AND AIMS: The causative molecular pathways underlying the pathogenesis of coeliac disease are poorly understood. To unravel novel aspects of disease pathogenesis, we used microarrays to determine changes in gene expression of duodenal biopsies. METHODS: cDNA microarrays representing 19 200 genes were used to compare gene expression profiles of duodenal biopsies from 15 coeliac disease patients with villous atrophy (Marsh III) and seven control individuals with normal biopsies (Marsh 0). In addition, the specific effect of gluten was studied by comparing the expression profiles of Marsh III lesions of seven patients exposed to gluten with four patients on a gluten free diet. RESULTS: Comparing Marsh III with Marsh 0 lesions identified 109 genes that differed significantly (p<0.001) in expression levels between patients and controls. A large number of these genes have functions in proliferation and differentiation pathways and might be important for correct development of crypt-villous units. Alterations in these pathways may lead to the characteristic hyperplasia and villous atrophy seen in coeliac disease. The analyses also revealed 120 differentially expressed genes (p<0.005) when comparing patients on a gluten free diet with those exposed to gluten. These genes further strengthen our observation of increased cell proliferation in the presence of gluten. CONCLUSIONS: Our study provides new candidate genes in the pathogenesis of coeliac disease. Based on our results, we hypothesise that villous atrophy in coeliac disease patients is due to failure in cell differentiation. These genes are involved in pathways not previously implicated in coeliac disease pathogenesis and they may provide new targets for therapy.

Adult↗
PubMed2003

[Alpha]B-crystallin genotype has impact on the multiple sclerosis phenotype.

BACKGROUND: Both multiple sclerosis (MS) susceptibility and MS clinical phenotype are in part genetically determined. [Alpha]B-crystallin is a candidate autoantigen in MS, and there are three polymorphisms in the promoter region of the encoding gene (CRYAB): at positions -C249G, -C650G, and -A652G. METHODS: These polymorphisms were studied in sporadic cases of MS, assessing disease susceptibility, clinical phenotype, and MRI appearance. RESULTS: The CRYAB polymorphisms influenced susceptibility as well as disease expression in MS. CONCLUSION: Carriers of the rare allele CRYAB-650*C had an increased likelihood of a noninflammatory, neurodegenerative phenotype characterized by a relatively rapid, primary progressive clinical disease course.

Adult↗
PubMed2003

Association between polymorphisms in the human chemokine receptor genes CCR2 and CX3CR1 and rheumatoid arthritis.

Cell trafficking into the rheumatoid synovium is thought to play an important role in the inflammation seen in rheumatoid arthritis. Chemokine receptors play a central role in this process, and several common variants are known, including the CCR2 variant, CCR2-64I, and two variants of the CX3CR1 gene, V249I and T280M. All three variants result in functional amino acid substitutions. We studied the association of these chemokine receptor variants with susceptibility to and severity of rheumatoid arthritis in two Dutch patient populations; 282 consecutive rheumatoid arthritis patients from a rheumatology outpatient clinic, and a cohort of 101 female rheumatoid arthritis patients, followed closely for a 12-year period, from whom hand and feet X-rays taken at three year intervals were scored and analyzed in this study. Although there was a trend towards increased severity of disease in patients carrying CX3CR1 variants, this was not independent of known risk factors. We found no evidence for a significant independent role for the CCR2 and CX3CR1 variants in the susceptibility to or severity of rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed2003

CARD15 gene mutations are not associated with ankylosing spondylitis.

An insertion mutation at nucleotide 3020 (3020insC) and a missense mutation G2722C in the CARD15 gene on chromosome 16p have been reported to be associated with Crohn's disease (CD). The protein encoded by the CARD15 gene is expressed in peripheral monocytes and regulates apoptosis and NF-kappaB activation, factors which play an important role in inflammation. Since CD and ankylosing spondylitis (AS) are interrelated disorders, we have investigated whether these mutations in the CARD15 gene are also associated with AS. We studied 113 unrelated AS patients and 152 unrelated healthy controls. No significant differences were found between patients and controls in the prevalence of the insertion 3020insC mutation and the G2722C missense mutation, OR = 1.36, 95% CI: 0.27-6.84, P = 0.70 and OR = 0.58; 95% CI: 0.18-1.94; P = 0.38, respectively. We conclude that the insertion 3020insC mutation and the G2722C missense mutation in the CARD15 gene are not involved in the susceptibility to AS.

Adolescent↗
PubMed2003

Signal transducer and activator of transcription 6 gene G2964A polymorphism and inflammatory bowel disease.

Signal transducer and activator of transcription 6 (STAT6) is a key transcription factor involved in interleukin 4 (IL-4) and IL-13-mediated Th2 response. The STAT6 gene is located on chromosome 12q13.3-14.1 (IBD2 region) and is therefore a positional and functional candidate gene for study in inflammatory bowel disease. We investigated the G2964A polymorphism in the 3' untranslated region of the STAT6 gene in Dutch patients with inflammatory bowel disease and healthy controls. The G2964A polymorphism in the STAT6 gene was genotyped in 141 unrelated Dutch Caucasian patients with ulcerative colitis, 183 patients with Crohn's disease and 173 healthy individuals by PCR and the amplification-created restriction site method. Patients with Crohn's disease were classified according to the Vienna classification and the patients with ulcerative colitis were classified with the age at onset, extent of disease and colectomy. We did not find significant differences in genotype and allele frequencies of the G2964A polymorphism in the STAT6 gene between ulcerative colitis, Crohn's disease and healthy controls. Subgroups of the patients with Crohn's disease classified according to the Vienna classification and those with ulcerative colitis classified according to age of onset, disease extension and colectomy did not differ in the distribution of this polymorphism. The STAT6 G2964A gene polymorphism is not involved in the overall susceptibility or in determining the phenotype of IBD.

Adult↗
PubMed2003

Association of interleukin 1 gene family polymorphisms with duodenal ulcer disease.

Cytokine genes taking part in the immunological response to Helicobacter pylori infection are good candidates to study for genetic predisposition to duodenal ulcer disease (DU). Among cytokines, interleukin (IL)-1beta and its natural specific inhibitor, the interleukin-1 receptor antagonist, are cytokines that play a key role in regulating gastric acid secretion and modulating the immune response in the gastrointestinal mucosa. We aimed to investigate whether polymorphisms in the IL-1B and IL-1RN genes are involved in the susceptibility to duodenal ulcer. DNA from 131 unrelated Spanish Caucasian patients with DU and 105 ethnically matched healthy controls was typed for the IL-1B-511, IL-1B-31, and IL-1B + 3954 gene polymorphisms, and the VNTR polymorphism in intron 2 of the IL-1RN gene by polymerase chain reaction (PCR)-based methods and TaqMan assays. H. pylori status and non-steroidal anti-inflammatory drugs (NSAIDs) use was determined in all patients and controls. Logistic regression analysis identified H. pylori infection (OR: 9.74; 95%CI = 3.53-26.89) and NSAIDs use (OR: 8.82; 95%CI = 3.51-22.17) as independent risk factors for DU. In addition, the simultaneous carriage of IL-1RN*2, IL-1B-511*C, IL-1B-31*T and IL-1B + 3954*C alleles was a genetic risk factor for DU in patients with H. pylori infection (OR: 3.22; 95%CI = 1.09-9.47). No significant differences in IL-1RN and IL-1B genotypes were found when patients were categorized according to gender, age of onset, smoking habit, NSAIDs use, type of complication and positive family history. Our results provide further evidence that host genetic factors play a key role in the pathogenesis of duodenal ulcer.

Adolescent↗
PubMed2003

IL12B and IRF1 gene polymorphisms and susceptibility to celiac disease.

Celiac disease (CD) is a common gastro-intestinal disorder resulting from permanent intolerance to wheat gliadins and related proteins in rye and barley. In addition to the strong genetic association with HLA-DQ2 and HLA-DQ8, a genetic region on chromosomes 5 (CELIAC2) has been identified that harbours a susceptibility gene for CD. The gene(s) responsible for this association, however, remains to be identified. In the present study we evaluated polymorphisms in the genes encoding interleukin-12 p40 (IL12B) and interferon regulatory factor 1 (IRF1). Both genes are located in the celiac2 region, and have key roles in inducing interferon (IFN)-gamma secreting T helper 1 (Th1) cells, one of the immunological hallmarks of CD. The frequencies of a TaqI gene polymorphism in the 3' UTR of IL12B and a HinfI gene polymorphism in the 3' UTR of IRF1 were studied in 258 Dutch CD patients and 237 ethnically matched healthy controls. The transmission of the polymorphic variants from parents to affected child was determined in 123 families with at least one affected child. The frequencies of the IL12B TaqI gene polymorphism and the IRF1 HinfI gene polymorphism did not differ significantly between patients and controls. In addition, in the family study, no deviation from the expected transmission from parents to affected child of any of the polymorphic variants was found. The IL12B TaqI and the IRF1 HinfI gene polymorphisms do not appear to be involved in susceptibility to CD. Further studies on the factors that drive the Th1 immunopathology in CD are required.

3' Untranslated Regions↗