Polymorphisms of the vitamin D receptor gene in Crohn's disease / Polimorfismos do gene do receptor de vitamina D na doença de Crohn

Introduction: Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory conditions of the gastrointestinal tract. Studies have shown that polymorphisms of the vitamin D receptor (VDR) gene may help elucidate the pathogenesis of CD. Objectives: To analyze the role of VDR gene polymorphisms (ApaI, BsmI, FokI, and TaqI) in the development of CD. Methods: The present study is a systematic review with meta-analysis. a total of 50 articles in English and Portuguese published from 2000 to 2020 were selected from 3 databases. The relationship between CD and the VDR gene was addressed in 16 articles. Results: The TaqI polymorphism was analyzed in 3,689 patients and 4,645 control subjects (odds ratio [OR]=0.948; 95% confidence interval [95%CI]=0.851-1.056; p=0.3467). The ApaI polymorphism was studied in 3,406 patients and 4,415 control subjects (OR=1,033; 95%CI=0.854-1.250; p=0.7356). For FokI polymorphism, there were 2,998 patients and 4,146 control subjects (OR=0.965; 95%CI=0.734-1.267; p=0.7958). Lastly, the BsmI polymorphism was analyzed in 2,981 patients and 4,477 control subjects (OR=1,272; 95%CI=0.748-2.161; p=0.3743). Conclusion: These four VDR gene polymorphisms were not associated with CD. Therefore, further studies with larger samples are required to corroborate or rectify the conclusions from the present meta-analysis. (AU)

Introdução: A doença de Crohn (DC) e a retocolite ulcerativa (RU) são condições inflamatórias crônicas do trato gastrointestinal. Estudos indicam que os polimorfismos do gene do receptor de vitamina D (RVD) são promissores para a patogênese da DC. Objetivos: Avaliar papel dos os polimorfismos do gene do RVD (ApaI, BsmI, FokI e TaqI) no desenvolvimento da DC. Métodos: Trata-se de uma revisão sistemática com metanálise. Foram identificados 50 artigos em inglês e português publicados entre 2000 a 2020 em 3 bases de dados. Destes, foram selecionados 16 artigos que contemplavama relação entre a DC e o genedo RVD. Resultados: Para o polimorfismo TaqI, a amostra foi composta por 3.689 pacientes e 4.645 controles (razão de probabilidade [RP]=0,948; intervalo de confiança de 95% [IC95%]=0,851-1,056; p=0,3467). Para o polimorfismo ApaI, 3.406 pacientes e 4.415 controles (RP=1,033; IC95%=0,854-1,250; p=0,7356). Para o polimorfismo FokI, 2.998 pacientes e 4.146 controles (RP=0,965; IC95%=0,734-1,267; p=0,7958). E, para o polimorfismo BsmI, 2.981 pacientes e 4.477 controles (RP =1,272; IC95%=0,748-2,161; p=0,3743). Conclusão: Esses quatro polimorfismos do gene do RVD não apresentaram associação coma DC. Logo, sugere-se a realização de mais estudos com amostras maiores a fimde corroborar ou retificar a conclusão desta metanálise. (AU)

Epidemiología y fenotipo de la enfermedad de Crohn en un hospital de referencia en Lima Perú / Epidemiology and phenotype of Crohn's disease in a reference hospital in Lima Peru

RESUMEN La enfermedad de Crohn (EC) es una patología inflamatoria crónica del tracto digestivo con gran impacto en la calidad de vida de los pacientes. La epidemiología mundial está cambiando en los últimos años y su prevalencia está aumentando en Latinoamérica. Objetivo: Evaluar las características epidemiológicas, fenotipo, curso clínico, diagnóstico y tratamiento de la EC. Materiales y métodos: Estudio observacional, descriptivo, retrospectivo de pacientes con diagnóstico de EC desde enero 2004 a diciembre 2019 en el servicio de gastroenterología del Hospital Nacional Guillermo Almenara Irigoyen, LimaPerú. Resultados: Se incluyó 55 pacientes, con edad promedio de 56 ± 8,2 años. Predominio masculino (62%). El tiempo promedio de diagnóstico fue de 18 ± 6,1 meses. Los síntomas más frecuentes fueron: dolor abdominal 72,7% y baja de peso 60%. Las manifestaciones extraintestinales se presentaron en 20%. La localización ileal (36,4%) fue la más frecuente, seguida de la colónica (32,7%). Predominó el fenotipo inflamatorio en la mitad de los pacientes, seguido de estenosante en 25,5%. La actividad clínica y endoscópica más frecuente fue moderada. Para el tratamiento de inducción y mantenimiento, los corticoides sistémicos y la terapia biológica con anti-TNF fueron los más utilizados respectivamente. Aproximadamente un tercio de pacientes requirieron cirugía durante la evolución de la enfermedad. La mortalidad fue del 5,4%. Conclusiones: La EC es una enfermedad cada vez más frecuente en nuestro país, con características epidemiológicas y fenotípicas que difieren de otros continentes.

ABSTRACT Crohn's disease (CD) is a chronic inflammatory pathology of the digestive tract with great impact on the quality of life of patients. Global epidemiology is changing in recent years and its prevalence is increasing in Latin America. Objective: To evaluate the epidemiological characteristics, phenotype, clinical course, diagnosis and treatment of CD. Materials and methods: Retrospective, descriptive, observational study of patients diagnosed with CD from January 2004 to December 2019 in the gastroenterology service of the Guillermo Almenara Irigoyen National Hospital, Lima-Peru. Results: 55 patients with an average age of 56 ± 8.2 years were included. Male predominance (62%). The average diagnosis time was 18 ± 6.1 months. The most frequent symptoms were: abdominal pain 72.7% and weight loss 60%. Extraintestinal manifestations occurred in 20%. The ileal location (36.4%) was the most frequent, followed by colonic (32.7%). The inflammatory phenotype predominated in half of the patients, followed by stenosing in 25.5%. The most frequent activity clinical and endoscopic was moderate. For induction and maintenance treatment, systemic corticosteroids and biological therapy with anti-TNF were the most widely used, respectively. Approximately a third of patients required surgery during the evolution of the disease. Mortality was 5.4%. Conclusions: CD is an increasingly frequent disease in our country, with epidemiological and phenotypic characteristics that differ from other continents.

Síndrome Bazex-Dupré-Christol: serie de casos / Bazex-Dupré-Christol syndrome: Case series

El síndrome de Bazex-Dupré-Christol es una genodermatosis ligada al cromosoma X, la cual se caracteriza por presentar hipotricosis congènita, hipohidrosis, atrofodermia folicular, múltiples quistes de millium y carcinomas basocelulares. Presentamos a una niña y su familia con este síndrome. La paciente y sus hermanos de 5 meses de edad y de 17 años de edad presentaban múltiples quistes de millium e hipotricosis de las cejas y el cuero cabelludo. Su hermano de 8 años presentaba quistes de millium y atrofodermia folicular. Su madre presentaba hipohidrosis, hipotricosis congènita del cuero cabelludo y las cejas, así como también una lesión tumoral en la región paranasal derecha compatible con carcinoma basocelular. Destacamos la importancia del diagnóstico y del seguimiento clínico de estos niños por la posibilidad de desarrollar carcinomas basocelulares.

Bazex-Dupré-Christol syndrome is an X-linked dominantly inherited disorder characterized by congenital hypotrichosis, hypohidrosis, follicular atrophoderma, multiple milia and basal cell carcinomas. We present a girl and her family with this syndrome. Our patient, her 5 month old brother and her 17 year old brother had multiple milia and scalp and eyebrows hypotrichosis. Her 8 year old brother had multiple milia and follicular atrophoderma. Her mother had hypohidrosis and congenital scalp and eyebrows hypotrichosis, as well as a right paranasal lesion suggestive of basal cell carcinoma. We emphasize the importance of precise diagnosis and clinical follow up of these patients due to the possibility of developing basal cell carcinomas.

Fasting abbreviation among patients submitted to oncologic surgery: systematic review / Abreviação do jejum entre pacientes submetidos à cirurgia oncológica: revisão sistemática

INTRODUCTION: The abbreviation of perioperative fasting among candidates to elective surgery have been associated with shorter hospital stay and decreased postoperative complications. OBJECTIVE: To conduct a systematic review from randomized controlled trials to detect whether the abbreviation of fasting is beneficial to patients undergoing cancer surgery compared to traditional fasting protocols. METHOD: A literature search was performed in electronic databases: MEDLINE (PubMed), SciELO, EMBASE and Cochrane, without time restriction. Were used the descriptors: "preoperative fasting", "cancer", "diet restriction" and "perioperative period". Randomized trials were included in adults of both sexes, with diagnosis of cancer. Exclusion criteria were: use of parenteral nutrition and publications in duplicate. All analyzes, selections and data extraction were done blinded manner by independent evaluators. RESULTS: Four studies were included, with a total of 150 patients, 128 with colorectal cancer and 22 gastric cancer. The articles were published from 2006 to 2013. The main outcome measures were heterogeneous, which impaired the unification of the results by means of meta-analysis. Compared to traditional protocols, patients undergoing fasting abbreviation with the administration of fluids containing carbohydrates had improvements in glycemic parameters (fasting glucose and insulin resistance), inflammatory markers (interleukin 6 and 10) and indicators of malnutrition (grip strength hand and CRP/albumin ratio), and shorter hospital stay. The methodological quality of the reviewed articles, however, suggests that the results should be interpreted with caution. CONCLUSION: The abbreviation of perioperative fasting in patients with neoplasm appears to be beneficial. .

INTRODUÇÃO: A abreviação do jejum perioperatório em pacientes candidatos à operações eletivas associa-se com menor tempo de internação hospitalar e diminuição de complicações pós-operatórias. OBJETIVO: Conduzir uma revisão sistemática a partir de ensaios clínicos randomizados controlados para detectar se a abreviação do jejum traz benefícios para indivíduos submetidos à cirurgia oncológica comparativamente aos protocolos de jejum tradicionais. MÉTODO: A busca na literatura foi realizada nas bases de dados eletrônicas: MEDLINE (Pubmed), Scielo, EMBASE e Cochrane, sem restrição de período. Utilizaram-se os descritores: "preoperative fasting", "cancer", "diet restriction" e "perioperative period". Foram incluídos ensaios clínicos randomizados, em indivíduos adultos, de ambos os sexos, com diagnóstico de câncer. Consideraram-se critérios de exclusão: uso de nutrição parenteral e publicações em duplicata. Todas as análises, seleções e extração dos dados foram feitas de maneira cega por avaliadores de forma independente. RESULTADOS: Foram incluídos quatro artigos, com total de 150 pacientes, sendo 128 com câncer colorretal e 22 câncer gástrico. Os artigos foram publicados no período de 2006 a 2013. Os desfechos principais foram heterogênios, o que impediu a unificação dos resultados por meio de metanálise. Comparativamente aos protocolos tradicionais, os indivíduos submetidos à abreviação do jejum com a administração de líquidos contendo carboidratos tiveram melhora nos parâmetros glicêmicos (glicemia de jejum e resistência a insulina), inflamatórios (interleucina 6 e 10) e nos marcadores de desnutrição (força do aperto de mão e razão PCR/albumina), assim como menor tempo de internação. A qualidade metodológica dos artigos avaliados, porém, sugere que os resultados sejam interpretados com cautela. CONCLUSÃO: A abreviação do jejum perioperatório em pacientes com neoplasias parece ser benéfica. .

Is Whole Exome Sequencing Clinically Practical in the Management of Pediatric Crohn's Disease?

BACKGROUND/AIMS: The aim of this study was to identify the profile of rare variants associated with Crohn's disease (CD) using whole exome sequencing (WES) analysis of Korean children with CD and to evaluate whether genetic profiles could provide information during medical decision making. METHODS: DNA samples from 18 control individuals and 22 patients with infantile, very-early and early onset CD of severe phenotype were used for WES. Genes were filtered using panels of inflammatory bowel disease (IBD)-associated genes and genes of primary immunodeficiency (PID) and monogenic IBD. RESULTS: Eighty-one IBD-associated variants and 35 variants in PID genes were revealed by WES. The most frequently occurring variants were carried by nine (41%) and four (18.2%) CD probands and were ATG16L2 (rs11235604) and IL17REL (rs142430606), respectively. Twenty-four IBD-associated variants and 10 PID variants were predicted to be deleterious and were identified in the heterozygous state. However, their functions were unknown with the exception of a novel p.Q111X variant in XIAP (X chromosome) of a male proband. CONCLUSIONS: The presence of many rare variants of unknown significance limits the clinical applicability of WES for individual CD patients. However, WES in children may be beneficial for distinguishing CD secondary to PID.

T300A GENETIC POLYMORPHISM: a susceptibility factor for Crohn?s disease? / Polimorfismo genético T300A: fator de susceptibilidade para doença de Crohn?

Context Crohn’s disease is characterized by a chronic and debilitating inflammatory disorder of the gastrointestinal tract. Several factors may contribute to its development. From extensive studies of the human genome, the polymorphism T300A of the gene ATG16L1 (autophagy-related 16-like 1) has been related to increased risk of developing this disease. Objectives Analyze the role of polymorphism T300A (rs2241880) in patients with Crohn’s disease. Methods 238 samples from (control group) and 106 samples from patients with Crohn’s disease recruited at five Southern Brazilian reference centers were evaluated. The genotyping consisted of the amplification via Polymerase Chain Reaction of the genomic segment encompassing T300A, followed by Restriction Fragment Length Polymorphism analysis. The amplicons and fragments were separated by agarose gel electrophoresis and confirmed under ultraviolet light. Results The genotype AG was more prevalent among patients and controls (50% vs 44.8%), followed by genotypes AA (26.4% vs 35.1%) and GG (23.6% vs 20.1%). The frequency of the allele G of the polymorphism T300A was higher in the group of patients with Crohn’s disease (48.6%) than in controls (42.4%), although not reaching statistical significance. Conclusions It was not possible to confirm the increased susceptibility on development of Crohn’s disease conferred by polymorphism T300A. .

Contexto A doença de Crohn caracteriza-se por uma desordem inflamatória, crônica e debilitante do trato gastrointestinal. Diversos fatores contribuem para seu desenvolvimento. A partir da realização de estudos amplos do genoma, o polimorfismo T300A do gene ATG16L1 (autophagy-related 16-like 1) tem sido relacionado com aumento de susceptibilidade ao desenvolvimento desta doença. Objetivos Analisar a incidência do polimorfismo T300A (rs2241880) em pacientes com doença de Crohn. Métodos Foram analisadas 238 amostras de doadores de sangue (grupo controle) e 106 amostras de pacientes com doença de Crohn, procedentes de cinco centros. A genotipagem consistiu em amplificação do segmento gênico T300A, via reação em cadeia da polimerase, seguidos da análise de polimorfismo de comprimentos dos fragmentos de restrição. Os amplicons e fragmentos foram separados via eletroforese em gel de agarose e visualizados sob luz ultravioleta. Resultados O genótipo AG foi mais prevalente entre os pacientes e controles (50% vs 44,8%), seguido dos genótipos AA (26,4% vs 35,1%) e GG (23,6% vs 20,1%). A freqüência do alelo G do polimorfismo T300A foi maior no grupo de pacientes com doença de Crohn (48,6%) do que nos controles (42,4%), embora sem significância estatística. Conclusões Não foi possível confirmar o aumento de susceptibilidade à doença de Crohn conferido pelo polimorfismo T300A. .

Associação de polimorfismos nas sequências regulatórias dos genes HLA-G, IL-10 e TNF e a sua respectiva expressão gênica em lesões de mucosa em pacientes portadores de doença inflamatória intestinal / Association of HLA-G, IL-10 and TNF regulatory sequence polymorphisms and respective gene expression in biopsies of Brazilian patients with Inflammatory Bowel Disease

Fatores genéticos e imunológicos foram associados à patogenese da doença inflamatória intestinal (DII), ela inclui Retocolite Ulcerativa Idiopática (RCUI) e doença de Crohn (CD). A hiperresponsividade de celulas B e a autoreatividade de células T contribuem para a polarização da resposta imune Th1 em CD e Th2 em RCUI. Sítios polimórficos na região 3'não traduzida do gene HLA-G (completa) e região promotora dos genes IL-10 ( - 1082A/G e - 819C/T) e TNF (completa) foram associados a susceptibilidade a diversas doenças. Estudamos 217 portadores de DII e 249 doadores saudáveis, pareados por sexo e idade. A ascendência africana foi maior em RCUI e caucasiana em DC (p =0,005). Comparados aos controles, o genótipo HLA - G 14bpINS - INS (associado com baixa expressão de HLA - G) (p =0,006) e IL - 10 - 1082G - G (associado com alta expressão de IL - 10) (p =0,030) foram menos frequentes em pacientes com DC, possivelmente contribuindo para a polarização Th1, mas não foram encontradas diferenças nas frequências de TNF. Em RCUI, as frequências do alelo HLA-G +3003C (p =0,015) e genótipo +3003C-T (p =0,003) estavam aumentadas. Apesar da alta frequência do alelo T em africanos, após estratifica rmos por ascendência, o genótipo +3003C - T ainda estava mais frequente em pacientes com ascendência africana (p =0,012)...

Genetic and immunological factors have been associated with inflammatory bowel disease (IBD) pathogenesis, encompassing ulcerative colitis (UC) and Crohn's disease (CD).B cell hyperresponsiveness and T cell auto-reactivity have contributedto a Th1 polarization immune response in CD and a Th2 polarization in UC. Sincepolymorphic sites at the 3’untranslated region (3’UTR)...

Multidrug resistance 1 gene polymorphisms may determine Crohn's disease behavior in patients from Rio de Janeiro

OBJECTIVES: Conflicting data from studies on the potential role of multidrug resistance 1 gene polymorphisms in inflammatory bowel disease may result from the analysis of genetically and geographically distinct populations. Here, we investigated whether multidrug resistance 1 gene polymorphisms are associated with inflammatory bowel diseases in patients from Rio de Janeiro. METHODS: We analyzed 123 Crohn's disease patients and 83 ulcerative colitis patients to determine the presence of the multidrug resistance 1 gene polymorphisms C1236T, G2677T and C3435T. In particular, the genotype frequencies of Crohn's disease and ulcerative colitis patients were analyzed. Genotype-phenotype associations with major clinical characteristics were established, and estimated risks were calculated for the mutations. RESULTS: No significant difference was observed in the genotype frequencies of the multidrug resistance 1 G2677T/A and C3435T polymorphisms between Crohn's disease and ulcerative colitis patients. In contrast, the C1236T polymorphism was significantly more common in Crohn's disease than in ulcerative colitis (p = 0.047). A significant association was also found between the multidrug resistance 1 C3435T polymorphism and the stricturing form of Crohn's disease (OR: 4.13; p = 0.009), whereas no association was found with penetrating behavior (OR: 0.33; p = 0.094). In Crohn's disease, a positive association was also found between the C3435T polymorphism and corticosteroid resistance/refractoriness (OR: 4.14; p = 0.010). However, no significant association was found between multidrug resistance 1 gene polymorphisms and UC subphenotypic categories. CONCLUSION: The multidrug resistance 1 gene polymorphism C3435T is associated with the stricturing phenotype and an inappropriate response to therapy in Crohn's disease. This association with Crohn's disease may support additional pathogenic roles ...

Association Between Toll-Like Receptors/CD14 Gene Polymorphisms and Inflammatory Bowel Disease in Korean Population

The innate immune response in patients who develop inflammatory bowel disease (IBD) may be abnormal. However, the exact role of Toll-like receptors (TLRs) / CD14 gene in the pathogenesis of IBD has not been fully elucidated. We aimed to investigate the association between polymorphisms of TLR1, 2, 4, 6, and CD14 gene and susceptibility to IBD in Korean population. A total 144 patients of IBD (99 patients with ulcerative colitis, 45 patients with Crohn's disease) and 178 healthy controls were enrolled. Using a PCR-RFLP, we evaluated mutations of TLR1 (Arg80Thr), TLR2 (Arg753Gln and Arg677Trp), TLR4 (Asp299Gly and Thr399Ile), TLR6 (Ser249Pro) genes and the -159 C/T promoter polymorphism of CD14 gene. No TLR polymorphisms were detected in Korean subjects. T allele and TT genotype frequencies of CD14 gene were significantly higher in IBD patients than in healthy controls. In subgroup analysis, T allelic frequency was higher in pancolitis phenotype of ulcerative colitis. In Korean population, the promoter polymorphism at -159 C/T of the CD14 gene is positively associated with IBD, both ulcerative colitis and Crohn's disease.

La mutación R92Q del gen TNFRSF1A se asocia con manifestaciones extra-intestinales en la enfermedad de Crohn / The TNFRSF1A gene R92Q mutation is associated with extra-intestinal manifestations of Crohn’s disease

It has been suggested that the R92Q mutation of the tumour necrosis factor receptor superfamily 1A (TNFRS1A) gene may be implicated in different inflammatory disorders. The aim of this study was to establish the role of this mutation as a determinant of Crohn`s disease (CD) susceptibility and/or clinical phenotype. One hundred and sixty-five CD patients and 203 healthy controls were prospectively included. The frequency of individuals carrying the R92Q mutation was similar between CD patients (4.24 percent) and controls (4.43 percent) (OR: 0.95; 95 percent CI = 0.34-2.62). In the genotype-phenotype evaluation, the univariate analysis showed that extra-intestinal manifestations were positively associated with the presence of R92Q mutation (p = 0.025; OR: 5.56; 95 percent CI = 1.04-29.6). In the multivariate analysis, presence of R92Q mutation was independently associated to extra-intestinal manifestations of CD, specially cutaneous manifestations (p = 0.02; OR: 5.17, 95 percent CI = 1.07-24.8). The R92Q mutation of TNFRSF1A gene is not a determinant of CD susceptibility, but contributes to the appearance of extra-intestinal manifestations of the disease.

Se ha sugerido que la mutación R92Q del gen de la super-familia del receptor del factor de necrosis tumoral 1A (TNFRS1A) podría estar relacionada con diversos trastornos inflamatorios. El objetivo de este estudio fue determinar el papel de esta mutación como factor determinante de la susceptibilidad y/o fenotipo clínico de la enfermedad de Crohn (EC). Ciento sesenta y cinco pacientes con EC y 203 controles sanos fueron incluidos de manera prospectiva. La frecuencia de individuos portadores de la mutación R92Q fue similar entre los pacientes con EC (4,24 por ciento) y los controles (4,43 por ciento) (OR: 0,95; 95 por ciento IC = 0,34-2,62). En la evaluación genotipo-fenotipo, el análisis univariado indicó que las manifestaciones extra-intestinales estaban relacionadas con la presencia de la mutación R92Q (p = 0,025; OR: 5,56; 95 por ciento IC = 1,04-29,6). En el análisis multivariado, la presencia de la mutación R92Q estuvo relacionada de manera independiente con las manifestaciones extra-intestinales de la EC, especialmente manifestaciones cutáneas (p = 0,02; OR: 5,17, 95 por ciento IC = 1,07-24,8). La mutación R92Q del gen TNFRSF1A no es un factor determinante de susceptibilidad a EC, pero contribuye a la aparición de manifestaciones extra-intestinales de la enfermedad.

The TNF-α -308 polymorphism may affect the severity of Crohn's disease

OBJECTIVE: The goal of this project was to analyze the association between Crohn's disease, its clinical features, and the tumor necrosis factor alpha (TNF-α) -308 polymorphism. METHODS: This is a case-control and cross-sectional study that enrolled 91 patients with Crohn's disease and 91 controls. Patients with Crohn's disease were characterized according to the Montreal Classification, along with their clinical and surgical treatment history. Analysis of the TNF-α -308 polymorphism was performed using a commercial kit. A stratified analysis was applied using an OR (odds ratio) with a 95 percent confidence interval. The chi-square and Fisher's exact tests were utilized for analysis of the association between the polymorphism and the clinical features of Crohn's disease. RESULTS: The low producer predicted phenotype was present in 76.9 percent of Crohn's disease cases and 75.8 percent of controls (OR 0.94 [0.45-1.97]). The TNF2 allele and the high producer predicted phenotype were more frequent among patients with Crohn's disease penetrating behavior (p = 0.004). The TNF2 allele and the high producer predicted phenotype were also associated with a history of colectomy (p = 0.02), and the TNF2 allele was associated with small bowel resection (p = 0.03). CONCLUSIONS: The TNF-α -308 polymorphism appears to affect the severity of the disease. However, TNF-α -308 polymorphism does not appear to be important for the susceptibility in the development of Crohn's disease.

Crohn's disease in a Saudi outpatient population: is it still rare?

To determine the epidemiology of Crohn's disease [CD] in an outpatient clinic and compare it with data previously reported from different centers in the Kingdom of Saudi Arabia and outside. The medical records of all patients with CD seen in the clinic in the period from January 1993 through December 2007 were reviewed. The demographic, clinical data and methods of diagnosis were retrieved. Over a period of 15 years, we saw 133 Saudi patients with CD. They were predominantly young, with a median age of 26.2 years and male preponderance [2.3:1]. The final diagnosis was established within 1 week of presentation in 47% of the patients. The leading symptoms were abdominal pain [88%], diarrhea [70%], bloating [61%], rectal bleeding [50%], weight loss [33%], constipation [24%] and perianal disease [23%]. The diagnosis was established by endoscopy and histopathology. Ileocecal involvement was encountered in 40% of the patients. From the current study, it is obviously possible to diagnose a large proportion of patients with CD in a gastroenterology outpatient clinic. The data revealed a strikingly increased incidence of CD in a mainly young Saudi population in the past few years

Enfermedad de Crohn con compromiso cutáneo mucoso / Crohn disease with cutaneous mucosal involvement

Comunicamos dos casos de enfermedad de Crohn con compromiso cutáneo-mucoso; el primer paciente con lesiones del denominado "Crohn metastásico" en las piernas y el segundo con importante compromiso en áreas perineo-genital, osteomal y de mucosa bucal, que luego de la remisión de las mismas sufrió una vasculitis leucocitoclásica en miembros inferiores. Los granulomas característicos de la enfermedad de Crohn se hallaron en la pared intestinal y la piel de ambos pacientes.

Two cases of Crohn disease are reported, both with cutaneous-mucosal involvement. The first patient showed lesions of the so called "Metastatic Crohn disease" in the legs, whereas the second one presented severe compromise in the perinealgenital, osteomal and oral mucosae. After the remission of the above mentioned, the patient suffered from leucocytoclastic vasculitis in the lower limbs. In both cases, the typical granulomatous lesions of the Crohn disease were found both in the skin and intestinal wall.

Enfermedad inflamatoria intestinal: Una mirada inmunológica: [revisión] / Inflammatory bowel diseases: An immunological approach: [review]

Inflammatory bowel diseases (IBD) are inflammatory diseases with a multifactorial component that involve the intestinal tract. The two relevant IBD syndromes are Crohn's disease (CD) and ulcerative colitis (UC). One factor involved in IBD development is a genetic predisposition, associated to NOD2/CARD15 and Toll-like receptor 4 (TLR4) polymorphisms that might favor infectious enterocolitis that is possibly associated to the development of IBD. The identification of specific immunologic alterations in IBD and their relationship to the etiology of the disease is a relevant research topic. The role of intra and extracellular molecules, such as transcription factors and cytokines that are involved in the inflammatory response, needs to be understood. The relevance of immunologic molecules that might drive the immune response to a T helper (Th) 1, Th 2 or the recently described Th 17 phenotype, has been demonstrated in animal models and clinical studies with IBD patients. CD and UC predominantly behave with a Th 1 and Th 2 immune phenotype, respectively. Recently, an association between CD and Th 17 has been reported. The knowledge acquired from immunologic and molecular research will help to develop accurate diagnostic methods and efficient therapies.

Frequency of three common mutations of CARD15/NOD2 gene in Iranian IBD patients.

BACKGROUND: The CARD15/NOD2 gene, located on the pericentromeric region of chromosome 16 (IBD1) has been reported to have an association with IBD, especially Crohn's disease. Three common mutations of CARD15 are variably associated with Crohn's disease in different ethnic groups. We evaluated the frequency of these mutations (R702W, G908R and 1007fsinsC) in Iranian IBD patients and compared it with the healthy control population. METHODS: One hundred patients with ulcerative colitis, 40 patients with Crohn's disease, and 100 sex- and age-matched controls were enrolled from a tertiary center during a one-year period (2005-2006). The three mutations were assessed in DNA of leukocytes by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). RESULTS: The frequency of R702W mutation was significantly higher in Iranian patients with Crohn's disease (p< 0.001; OR 19.21; 95% CI 4.23-87.32) compared to healthy controls. No association was observed between the other mutations and Crohn's disease and none of these mutations was associated with ulcerative colitis. CONCLUSION: The R702W mutation of CARD15 gene was associated with Crohn's disease in the Iranian population.

HLA antigens and inflammatory bowel disease in a sample of Iraqi patients

This study investigated the association between HLA antigens and inflammatory bowel disease in 65 Iraqi patients [50 ulcerative colitis, 15 Crohn disease] compared with 67 matched controls. At HLA class I region, the patients showed significantly increased frequencies of A9 and B41 and a decrease of A11. Similar results were found when the clinical types were considered separately, except for A11, which was not significant. At HLA class II region, DR8 was significantly increased in the total patients, but the association was not maintained for ulcerative colitis or Crohn disease patients; instead Crohn disease was positively associated with DQ1. Comparing the clinical types revealed a significant difference in the antigen B16, suggesting that B16 is a differentiating marker in the disease

Clinical applications of NOD2/CARD15 mutations in Crohn's disease / Aplicaciones clínicas de las mutaciones NOD2/CARD15 en la enfermedad de Crohn

The recent identification of the CARD15/NOD2 gene as a susceptibility locus for Crohn's disease represents an important step in the immunopathogenesis of inflammatory bowel disease. The gene explains about 20% of the genetic susceptibility CARD15 mutations are present in 30-50% of CD patients compared to 7-20% of healthy controls. The three risk alleles R702W, G908R and 1007fsInsC in NOD2 associated with susceptibility to Crohn's disease have demonstrated a remarkable amount of heterogeneity across ethnicities and populations, with regional variation across Europe. In non-Caucasian populations Crohn's disease continues to increase in incidence but this increase appears not to be a consequence of variation in NOD2. Genotype-phenotype analyses demonstrated an association of these mutations with ileum-specific disease and an increased incidence of the fibrostenotic phenotype. Although CARD15 variants do not predict response to the TNF alpha monoclonal antibodies, there are no data available on the possible influence of CARD15 mutations on response to other drugs. Screening for CARD15 mutations in order to identify high-risk individuals or to introduce an individualized disease management is therefore currently not recommended.

La reciente identificación del gen CARD15/NOD2 como locus de susceptibilidad para la enfermedad deCrohn representa un paso importante en la inmumopatogénesis de la enfermedad inflamatoria intestinal. El gen explica alrededor del 20% de la susceptibilidadgenética. Las mutaciones en CARD15 aparecen en 30-50% de los pacientes con enfermedad de Crohn en comparación con 7-20% en los controles sanos. Los tres alelos de riesgo R702W, G908R y 100fsInsC delNOD2 asociados con susceptibilidad a la enfermedad de Crohn han demostrado una significativa heterogeneidadentre diferentes grupos étnicos y poblaciones, con variaciones regionales en toda Europa. En las poblacionesno caucásicas la enfermedad de Crohn aumenta en incidencia pero esta incidencia no parece ser una consecuencia de variación del NOD2. Los análisis de genotipo/fenotipo demostraron una asociación deestas mutaciones con enfermedad de localización ileal y una mayor incidencia del fenotipo fibroestenosante. Si bien las variantes del CARD15 no predicen una respuesta a los anticuerpos monoclonales TNF alfa, no hay datos disponibles sobre la posible influencia de las mutaciones del CARD15 como respuesta a otras drogas. Por consiguiente no podemos recomendar exámenes para las mutaciones del CARD15 con el fin de identificar individuos de alto riesgo ni para introducir un manejo individualizado de la enfermedad.

frequency of three common mutations of CARD15/NOD2 gene in Iranian IBD patients

CARD15/NOD2 gene, located on the pericentromeric region of chromosome 16 [IBD1] has been reported to have an association with IBD, especially Crohn's disease [CD]. Many independent studies have shown a variable association between three common mutations of CARD 15, with Crohn's disease in different ethnic groups. Thus, raising the hypothesis that genetic and / or allelic heterogeneity may influence the relationship between CARD 15 and Crohn's disease. In the present study, we have investigated the frequency of three main mutations of CARD 15 gene [Arg 702 Trp, Gly 908 Arg and Leu 1007 fsinsC] in Iranian IBD patients and compared it with healthy control population. For this case-control study, 100 ulcerative colitis [UC], 40 Crohn's disease patients and 100 sex- age- and ethnicity-matched controls were enrolled from a teaching hospital during a one year period [2003-2004]. All three mutations were assessed on DNA of leukocyte cells, by PCR [Polymerase Chain Reaction] and RFLP [Restriction Fragment Length Polymorphism] methods. The mean age of UC, CD and healthy controls were 38.6 +/- 14.3, 36.6 +/- 14.1, and 38.6 +/- 14.2 years. Among the three evaluated CARD 15 gene mutations, the frequency of Arg702Trp mutation was significantly higher in Iranian patients with Crohn's disease [OR19.2; 95%CI:4.2-87.3, p<0.001]. None of these mutations were associated with ulcerative colitis. This study showed that Arg702Trp mutation of CARD 15 gene is probably associated with Crohn's disease in Iranian population; indicating that genetic polymorphisms may differ between populations

Frequency Analysis of NOD2 Gene Mutations in Korean Patients with Crohn's Disease / 대한소화기학회지

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.

Tumor Necrosis Factor-alpha and Interleukin-10 Gene Polymorphisms in Korean Patients with Inflammatory Bowel Disease / 대한소화기학회지

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.