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Putative Association (putative + association)
Selected AbstractsPutative association of a TLR9 promoter polymorphism with atopic eczemaALLERGY, Issue 7 2007N. Novak Background:, Toll-like receptors (TLR) play a pivotal role in the induction of first-line defense mechanisms of the innate immune system and trigger adaptive immune responses to microbial pathogens. Genetic variations in innate immunity genes have been reported to be associated with a range of inflammatory disorders. Deficiencies on the level of immunity receptors such as pathogen-recognition receptors are suspected to affect the maturation of our immune system and to avail thereby the high prevalence of atopic diseases and susceptibility of atopic patients to microbial infections. Aims of the study:, We evaluated TLR9 as susceptibility gene for atopic eczema (AE). Methods:, Analyses of four tag single-nucleotide polymorphisms in two panels of families containing a total of 483 parent-affected offspring trios as well as a cohort of 274 unrelated adult AE cases and 252 hypernormal population-based controls have been performed. Results:, In both family cohorts, polymorphism C-1237T, which is located within the promoter region of the TLR9 gene, was significantly associated with AE, in particular the intrinsic subtype of AE. No associations were seen in the case,control cohort. Luciferase reporter gene assays revealed significantly higher promoter activity of the TT allelic variant at this single nucleotide polymorphism site. Conclusion:, These observations suggest that the TLR9 promoter polymorphism C-1237T might affect AE susceptibility in particular in patients with the intrinsic variant of AE. [source] Enteroviruses and type 1 diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 6 2003Ruben Varela-Calvino Abstract The development of type 1 diabetes mellitus (T1DM) has been linked to exposure to environmental triggers, with Enteroviruses (EV) historically considered the prime suspects. Early serological studies suggested a link between EV infections and the development of T1DM and, though controversial, have been bolstered by more recent studies using more sensitive techniques such as direct detection of the EV genome by RT-PCR in peripheral blood. In this review, we consider the weight of evidence that EV can be considered a candidate trigger of T1DM, using three major criteria: (1) is EV infection associated with clinical T1DM, (2) can EV trigger the development of autoimmunity and (3) what would explain the putative association? Copyright © 2003 John Wiley & Sons, Ltd. [source] DNA repair polymorphisms associated with cytogenetic subgroups in B-cell chronic lymphocytic leukemia,GENES, CHROMOSOMES AND CANCER, Issue 9 2009Christina Ganster Genetic polymorphisms in DNA repair genes can affect the risk of developing different forms of cancer. Therefore, we have studied the putative association of seven single nucleotide polymorphisms (SNPs) in five DNA repair genes with the incidence of chronic lymphocytic leukemia (CLL). We included 461 CLL patients and the same number of age- and sex-matched controls. As chromosomal aberrations are important prognostic markers in CLL, we additionally correlated the SNPs with the occurrence of favorable and unfavorable cytogenetic aberrations in CLL patients. Patients with del(13q) as a sole aberration were allocated to the favorable cytogenetic risk group, and patients with del(17p) and/or del(11q) to the unfavorable cytogenetic risk group. All investigated SNPs were equally distributed between patients with the favorable cytogenetic aberration and controls. However, differences were observed in the distribution of rs13181 in ERCC2 between all CLL patients and controls. Moreover, the clearest differences were found for rs13181 in ERCC2 and rs25487 in XRCC1 between CLL patients with unfavorable cytogenetic aberrations and controls. These data suggest that inborn genetic polymorphisms may predict the outcome of CLL. © 2009 Wiley-Liss, Inc. [source] Relevance of translocation type in myxoid liposarcoma and identification of a novel EWSR1-DDIT3 fusionGENES, CHROMOSOMES AND CANCER, Issue 11 2007B. Bode-Lesniewska The clinical course of myxoid/round cell liposarcoma (MRCL) is characterized by frequent local recurrences and metastases at unusual sites. MRCLs carry specific translocations, t(12;16) or rarely t(12;22), linking the FUS or the EWSR1 gene with the DDIT3 gene, respectively. Nine FUS/DDIT3 and three EWSR1/DDIT3 variants of fusion transcripts have been described thus far. In search of prognostic markers for MRCL, we analyzed the translocation types of 31 patients and related them to the event free and overall survival. Using break-apart FISH and RT-PCR combined with DNA sequencing, we detected FUS/DDIT3 fusions in 30 sarcomas, while an EWSR1/DDIT3 translocation was identified in one tumor. FUS/DDIT3 type II (exons 5-2) was most commonly detected (20 cases), followed by type I (7-2) (7 cases) and type III (8-2) (3 cases). A single tumor carrying a t(12;22) translocation expressed a hitherto unknown EWSR1-DDIT3 fusion transcript (13-3) linking the complete RNA-binding domain of EWSR1 with a short piece of the 5,-UTR and the entire open reading frame of the DDIT3 gene. Interestingly, five of six patients with type I (7-2) FUS/DDIT3 fusions displayed local recurrences and/or metastatic spread within the first 3 years, generally requiring chemotherapeutical treatment (median disease-free survival 17 months). In contrast, 9 of 13 patients with type II FUS/DDIT3 translocations remained at 3 years disease-free (median disease-free survival 75 months). Since the total number of patients is still limited, further studies are required to verify a putative association of type I FUS/DDIT3 -fusion transcripts with a prognosis of MRCL. © 2007 Wiley-Liss, Inc. [source] A common variant in the patatin-like phospholipase 3 gene (PNPLA3) is associated with fatty liver disease in obese children and adolescents,,HEPATOLOGY, Issue 4 2010Nicola Santoro The genetic factors associated with susceptibility to nonalcoholic fatty liver disease (NAFLD) in pediatric obesity remain largely unknown. Recently, a nonsynonymous single-nucleotide polymorphism (rs738409), in the patatin-like phospholipase 3 gene (PNPLA3) has been associated with hepatic steatosis in adults. In a multiethnic group of 85 obese youths, we genotyped the PNLPA3 single-nucleotide polymorphism, measured hepatic fat content by magnetic resonance imaging and insulin sensitivity by the insulin clamp. Because PNPLA3 might affect adipogenesis/lipogenesis, we explored the putative association with the distribution of adipose cell size and the expression of some adipogenic/lipogenic genes in a subset of subjects who underwent a subcutaneous fat biopsy. Steatosis was present in 41% of Caucasians, 23% of African Americans, and 66% of Hispanics. The frequency of PNPLA3(rs738409) G allele was 0.324 in Caucasians, 0.183 in African Americans, and 0.483 in Hispanics. The prevalence of the G allele was higher in subjects showing hepatic steatosis. Surprisingly, subjects carrying the G allele showed comparable hepatic glucose production rates, peripheral glucose disposal rate, and glycerol turnover as the CC homozygotes. Carriers of the G allele showed smaller adipocytes than those with CC genotype (P = 0.005). Although the expression of PNPLA3, PNPLA2, PPAR,2(peroxisome proliferator-activated receptor gamma 2), SREBP1c(sterol regulatory element binding protein 1c), and ACACA(acetyl coenzyme A carboxylase) was not different between genotypes, carriers of the G allele showed lower leptin (LEP)(P = 0.03) and sirtuin 1 (SIRT1) expression (P = 0.04). Conclusion: A common variant of the PNPLA3 gene confers susceptibility to hepatic steatosis in obese youths without increasing the level of hepatic and peripheral insulin resistance. The rs738409 PNPLA3 G allele is associated with morphological changes in adipocyte cell size. (HEPATOLOGY 2010.) [source] Polymorphisms in fatty acid-binding protein-3 (FABP3) , putative association with type 2 diabetes mellitus,,HUMAN MUTATION, Issue 2 2003Hyoung Doo Shin Abstract Fatty acid-binding proteins (FABPs) play key roles as transport vehicles of fatty compounds throughout the cytoplasm. Human FABP3, one of the FABPs, is present in a wide variety of tissues with highest concentration in cardiac and skeletal muscle. In an effort to identify polymorphic markers in potential candidate genes for type 2 diabetes, we have sequenced the full gene of FABP3, including the ,1,500bp promoter region. Fourteen polymorphisms were identified in FABP3: two ins/dels, two STRs, and ten SNPs (two in promoter, nine in intron, two in 3'UTR, and one in the 3' end). Among identified polymorphisms, five common sites including c.-530underscore;-532delCTC, c.-345T>C, c.348+429(CA)9-18, c.246+1806G>C, and c.634+483delT were genotyped in subjects with type 2 diabetes mellitus and normal control (n=669). By logistic and multiple regression analysis, one insertion/deletion polymorphism in the 3' end (c.634+483delT) of FABP3 appeared to be weakly associated with increased risk of type 2 diabetes (OR=1.78,1.94, P=0.03,0.04) and waist/hip ratio (WHR) (P=0.03). © 2003 Wiley-Liss, Inc. [source] Inflammatory bowel disease in the setting of autoimmune pancreatitis,INFLAMMATORY BOWEL DISEASES, Issue 9 2009Karthik Ravi MD Abstract Background: Despite scattered case reports, the prevalence of inflammatory bowel disease (IBD) in patients with autoimmune pancreatitis (AIP) is unknown. We sought to better characterize the putative association between the conditions. Methods: Medical records of 71 patients meeting accepted criteria for AIP were reviewed to identify those with endoscopic and histological evidence of IBD. Colon samples in patients with both AIP and IBD were immunostained to identify IgG4-positive cells. Results: Four patients with AIP (5.6%) had a diagnosis of IBD: 3 had ulcerative colitis (UC) and 1 had Crohn's disease (CD). The diagnosis of IBD preceded or was simultaneous to that of AIP. Two AIP-UC patients treated for AIP with prednisone had a recurrence of AIP, and 1 required 6-mercaptopurine for long-term corticosteroid-sparing treatment. Two AIP-IBD patients underwent Whipple resections, and 1 had recurrent AIP. All 3 patients with UC presented with pancolitis, and 2 required colectomy. Colon samples from 1 patient with UC and 1 patient with CD were available for review. Increased numbers of IgG4-positive cells (10 per high-power field) were noted on the colon sample from the patient with UC. Conclusions: Almost 6% of patients with proven AIP had a diagnosis of IBD, compared to a prevalence of ,0.4%,0.5% in the general population, potentially implying a 12,15-fold increase in risk. Patients with both AIP and IBD may have increased extent and severity of IBD. The finding of IgG4-positive cells on colon biopsy suggests that IBD may represent an extrapancreatic manifestation of AIP. (Inflamm Bowel Dis 2009) [source] Depressive symptoms and suicidal ideation during isotretinoin treatment: a 12-week follow-up study of male Finnish military conscriptsJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 11 2009LMH Rehn Abstract Objective, To investigate the putative association between isotretinoin treatment and depressive symptoms or suicidal ideation among Finnish male military conscripts. Methods, Consecutive acne patients were enrolled into an uncontrolled, prospective 12-week follow-up study conducted at the Central Military Hospital, Helsinki, Finland. Of the 135 patients prescribed isotretinoin, 126 (93.3%) completed the follow-up. Depression and suicidal ideation were investigated with the Beck Depression Inventory (BDI) at baseline, weeks 4,6, and weeks 10,12. Results, BDI mean score was low at baseline and declined further significantly (p < 0.001) during the follow-up from 3.0 (SD 3.948) to 1.8 (SD 3.783) among patients on isotretinoin. Moreover, the proportion of patients with clinically significant depressive symptoms (BDI , 10) declined non-significantly from 7.1 % to 3.2 %. Suicidal ideation was reported by 17 (13.5 %) patients at baseline and 9 (7.1%) patients at the end of the follow-up (NS). During the follow-up, one non-depressed patient attempted suicide while intoxicated by alcohol. Conclusion, On group level, isotretinoin seems not to be typically associated with treatment-emergent depression or suicidal ideation among young men. However, the possibility that individual patients may be susceptible for mood effects of isotretinoin as a rare idiosyncratic reaction can not be excluded. [source] Length variability and interspersion patterns of the HRAS1 minisatellite: a new approach for the reconstruction of human population relationshipsANNALS OF HUMAN GENETICS, Issue 4 2001A. VEGA During recent years the HRAS1 minisatellite has been analysed by several authors because of its putative association with cancer susceptibility. The aim of this report is to test the usefulness of this minisatellite in investigating human population relationships. We have studied 370 chromosomes from two well-differentiated populations: Galicia (North-west Iberia) and South-east Africa, as well as available data on allele length gene frequencies. The fragment analysis results show a strong tendency to differentiate between non-African and African populations. In spite of the usefulness of fragment analysis, the minisatellite variant repeat (MVR) approach of the HRAS1 minisatellite appears to be a more powerful method for use in human population studies, due to the high level of diversity of its interspersion pattern structures. In addition, this approach has allowed us to define some new structural characteristics of this minisatellite. Four different major groups of human HRAS1 minisatellite alleles could be distinguished following a structural criterion based on the MVR code. Furthermore, the characterisation of the HRAS1 minisatellite in chimpanzees revealed clear differences when compared to humans, not only with respect to the allele size but also to the internal structure. [source] Association of psoriasis to PGLYRP and SPRR genes at PSORS4 locus on 1q shows heterogeneity between Finnish, Swedish and Irish familiesEXPERIMENTAL DERMATOLOGY, Issue 2 2009Kati Kainu Abstract:, A susceptibility locus for psoriasis, PSORS4, has been mapped to chromosome 1q21 in the region of the epidermal differentiation complex. The region has been refined to a 115 kb interval around the loricrin (LOR) gene. However, no evidence of association between polymorphisms in the LOR gene and psoriasis has been found. Therefore, we have analysed association to three candidate gene clusters of the region, the S100, small proline-rich protein (SPRR) and PGLYRP (peptidoglycan recognition protein) genes, which all contain functionally interesting psoriasis candidate genes. In previous studies, the SPRR and S100 genes have shown altered expression in psoriasis. Also polymorphisms in the PGLYRP genes have shown to be associated with psoriasis. We genotyped altogether 29 single nucleotide polymorphisms (SNPs) in 255 Finnish psoriasis families and analysed association with psoriasis using transmission disequilibrium test. A five-SNP haplotype of PGLYRP SNPs associated significantly with psoriasis. There was also suggestive evidence of association to SPRR gene locus in Finnish families. To confirm the putative associations, selected SNPs were genotyped also in a family collection of Swedish and Irish patients. The families supported association to the two gene regions, but there was also evidence of allelic heterogeneity. [source] | |||||||||||||