Novel genetic markers in inflammatory bowel disease

Genetic factors play a significant role in determining inflammatory bowel disease(IBD)susceptibility.Epidemiologic data support genetic contribution to the pathogenesis of IBD,which include familial aggregation,twin studies,racial and ethnic differences in disease prevalence.Linkage studies have identified several susceptibility genes contained in different genomic regions named IBD1 to IBD9.Nucleotide oligomerization domain(NOD2)and human leukocyte antigen(HLA)genes are the most extensively studied genetic regions(IBD1 and IBD3 respectively)in IBD.Mutations of the NOD2 gene are associated with Crohn's disease(CD)and several HLA genes are associated with ulcerative colitis(UC)and CD.Toll like receptors(TLRs)have an important role in the innate immune response against infections by mediating recognition of pathogen-associated microbial patterns.Studying single-nucleotide polymorphisms(SNPs)in molecules involved in bacterial recognition seems to be essential to define genetic backgrounds at risk of IBD.Recently,numerous new genes have been identified to be involved in the genetic susceptibility to IBD:NOD1/Caspase-activation recruitment domains 4(CARD4),Chemokine ligand 20(CCL20),IL-11,and IL-18 among others.The characterization of these novel genes potentially will lead to the identification of therapeutic agents and clinical assessment of phenotype and prognosis in patients with IBD.

Role of the HLA-DQ locus in the development of chronic gastritis and gastric carcinoma in Mexican patients

AIM： To determine the HLA-DQ locus in Mexican patients with Chronic gastritis and gastric adenocarcinoma.METHODS： Oligotyping for HLA-DQ locus was performed in 45 Mexican patients with chronic gastritis and 13 Mexican patients with diffuse-type gastric adenocarcinoma, and was then compared with 99 clinically healthy unrelated individuals. H pylori infection and CagA status were assessed in patients by enzyme-linked immunosorbent assay （EUSA） method. RESULTS： We found a significant increased frequency of HLA-DQBI＊0401 allele in Hpylori-positive patients with chronic gastritis when compared with healthy subjects [19 vs 0%, P = 1 × 10^-7, odds ratio （OR） = 4.96; 95% confidence interval （95% CI）, 3.87-6.35]. We also found a significant increased frequency of HLA-DQBI＊0501 in patients with diffuse-type gastric carcinoma in comparison with healthy individuals （P = 1 × 10^4, OR = 13.07; 95% CI, 2.82-85.14）.CONCLUSION： HLA-DQ locus may play a different role in the development of H pylori-related chronic gastritis and difffuse-type gastric adenocarcinoma in the Mexican Mestizo population.

Factors that influence outcome in non-invasive and invasive treatment in polycystic liver disease patients

AIM: To evaluate the factors that influence outcome of both non-invasive and invasive treatment of polycystic liver disease. METHODS: Analysis of clinical files of patients with complete follow-up from July 1986 to June 2006. RESULTS: Forty-one patients (male, 7; female, 34), 47.8 ± 11.9 years age, and 5.7 ± 6.7 years follow-up, were studied. Alkaline phosphatase (AP) elevation (15% of patients) was associated with the requirement of invasive treatment (IT, P = 0.005). IT rate was higher in symptomatic than non-symptomatic patients (65.4% vs 14.3%, P = 0.002), and in women taking hormonal replacement therapy (HRT) (P = 0.001). Cysts complications (CC) were more frequent (22%) in the symptomatic patients group (P = 0.023). Patients with body mass index (BMI) > 25 (59%) had a trend to complications after IT (P = 0.075). Abdominal pain was the most common symptom (56%) and indication for IT (78%). Nineteen patients (46%) required a first IT: 12 open fenestration (OF), 4 laparoscopic fenestration (LF) and 3 fenestration with hepatic resection (FHR). Three required a second IT, and one required a third procedure. Complications due to first IT were found in 32% (OF 16.7%, LF 25%, FHR 66.7%), and in thesecond IT in 66.7% (OF 100%). Follow-up mortality rate was 0. CONCLUSION: Presence of symptoms, elevated AP, and CC are associated with IT requirement. HRT is associated with presence of symptoms and IT requirement. Patients with BMI > 25 have a trend be susceptible to IT complications. The proportions of complications are higher in FHR and second IT groups. RS is more frequent after OF.

Basic and clinical aspects of osteoporosis in inflammatory bowel disease

Low bone mineral density and the increased risk of fracture in gastrointestinal diseases have a multifactorial pathogenesis. Inflammatory bowel disease （IBD） has been associated with an increased risk of osteoporosis and osteopenia and epidemiologic studies have reported an increased prevalence of low bone mass in patients with IBD. Certainly, genetics play an important role, along with other factors such as systemic inflammation, malnutrition, hypogonadism, glucocorticoid therapy in IBD and other lifestyle factors. At a molecular level the proinflammatory cytokines that contribute to the intestinal immune response in IBD are known to enhance bone resorption. There are genes influencing osteoblast function and it is likely that LRP5 may be involved in the skeletal development. Also the identification of vitamin D receptors （VDRs） and some of its polymorphisms have led to consider the possible relationships between them and some autoimmune diseases and may be involved in the pathogenesis through the exertion of its immunomodulatory effects during inflammation. Trying to explain the physiopathology we have found that there is increasing evidence for the integration between systemic inflammation and bone loss likely mediated via receptor for activated nuclear factor kappa-B （RANK）, RANK-ligand, and osteoprotegerin, proteins that can affect both osteoclastogenesis and T-cell activation. Although glucocorticoids can reduce mucosal and systemic inflammation, they have intrinsic qualities that negatively impact on bone mass. It is still controversial if all IBD patients should be screened, especially in patients with preexisting risk factors for bone disease. Available methods to measure BMD include single energy x-ray absorptiometry, DXA, quantitative computed tomography （QCT）, radiographic absorptiometry, and ultrasound.DXA is the establish method to determine BMD, and routinely is measured in the hip and the lumbar spine. There are several treatments options that have proven their effectiveness, while new emergent therapies such as calcitonin and teriparatide among others remain to be assessed.