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Authors: Sipos, Ferenc | Galamb, Orsolya | Wichmann, Barnabás | Krenács, Tibor | Tóth, Kinga | Leiszter, Katalin | Műzes, Györgyi | Zágoni, Tamás | Tulassay, Zsolt | Molnár, Béla
Article Type: Research Article
Abstract: A molecular diagnostic assay using easily accessible peripheral blood would greatly assist in the screening and diagnosis of ulcerative colitis (UC) and Crohn's disease (CD). Transcriptional profiles in blood/biopsy samples from 12 UC (6/12), 9 CD (5/9), 6 non-inflammatory bowel disease (non-IBD) colitis (6/0), and 11 healthy (11/11) patients were assessed by Affymetrix HGU133Plus2.0 microarrays. Prediction analysis of microarrays, discriminant and ROC analyses were performed, the results were validated by RT-PCR and …immunohistochemistry using also an independent set of samples (15 blood samples, 45 biopsies). A set of 13 transcripts was differentially expressed in IBD, non-IBD controls and healthy blood samples (100% specificity and sensitivity). Validated difference was found in 16 transcripts between UC, non-IBD and normal blood, and 4 transcripts between CD, non-IBD and normal samples. UC and CD blood cases could be also distinguished by 5 genes with 100% specificity and sensitivity. Some disease associated alterations in blood transcripts were also detected in colonic tissue. IBD subtypes may be discriminated from non-IBD (diverticulitis, infective and ischemic colitis) in vitro from peripheral blood by screening for differential gene expression revealed in this study. Transcriptional profile alterations in peripheral blood can be located in diseased colon. Show more
Keywords: IBD, blood, gene expression profile, screening, tissue microarray
DOI: 10.3233/DMA-2011-0758
Citation: Disease Markers, vol. 30, no. 1, pp. 1-17, 2011
Authors: Guzmán-Flores, Juan Manuel | Muñoz-Valle, José Francisco | Sánchez-Corona, José | Cobián, José G. | Medina-Carrillo, Leopoldo | G. García-Zapién, Alejandra | Cruz-Quevedo, Edhit G. | Flores-Martínez, Silvia Esperanza
Article Type: Research Article
Abstract: The {association} between some Tumor necrosis factor-alpha (TNF-α) promoter polymorphisms and Type 2 diabetes mellitus (T2DM) remains controversial. Ethnic differences may play a role in these conflicting results. The aim of this study was to investigate the association between −308G/A and −238G/A polymorphisms located in the promoter region of the TNF-α gene and T2DM in Mexican mestizo patients. Nine hundred four individuals (259 patients with T2DM and 645~controls) were genotyped for the …−308G/A and −238G/A polymorphisms by PCR--RFLP. We found that the −238A allele increased the risk of developing T2DM in Mexican patients (OR=1.57, 95% CI: 1.07–2.29; p=0.018). Moreover, we found that the frequency of the GA haplotype (created by the −308G and −238A alleles) was significantly increased in patients with T2DM when compared with controls (OR =1.56, 95% CI: 1.05–2.31; p=0.026). Our results suggest that the −238G/A polymorphism and a specific haplotype (GA) are genetic risk factors for the development of T2DM in Mexican population. Show more
Keywords: Haplotype, Mexican patients, polymorphism, TNF-alpha, Type 2 diabetes mellitus
DOI: 10.3233/DMA-2011-0759
Citation: Disease Markers, vol. 30, no. 1, pp. 19-24, 2011
Authors: Ledezma-Lozano, I.Y. | Padilla-Martínez, J.J. | Leyva-Torres, S.D. | Parra-Rojas, I. | Ramírez-Dueñas, M.G. | Pereira-Suárez, Ana Laura | Rangel-Villalobos, H. | Ruiz-Quezada, S.L. | Sánchez-Hernández, P.E. | Muñoz-Valle, J.F.
Article Type: Research Article
Abstract: Objective: Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology in which inflammatory pathology involves T cell activation and the CD28 costimulatory molecule involved in T cell presentation. The gene includes the CD28 IVS3 +17T/C polymorphism that could be associated with susceptibility to RA whereas the soluble concentrations of CD28 (sCD28) could be related to clinical activity. Methods: We investigated the CD28 IVS3 +17T/C polymorphism in 200 RA patients and 200 healthy subjects …(HS). {Furthermore, we quantified the sCD28 concentrations in 77 samples of each group.} We applied indexes focused to determine the activity and disability (DAS28 and Spanish HAQ-DI, respectively) in RA patients. Results: RA patients had significantly higher frequencies of the CD28 T allele compared to HS (p = 0.032 OR = 1.59, C.I. 1.02–2.49). In addition, the IVS3 +17 T/T genotype frequency was also increased in RA vs. HS (p = 0.026). The RA patients showed higher sCD28 serum levels than HS (p = 0.001). Carriers of the T/T genotype in RA patients showed higher sCD28 levels than C/C carriers (p =0.047). In addition, a correlation between sCD28 and Spanish HAQ-DI (correlation, 0.272; p =0.016), was found. Conclusion: The T allele in CD28 IVS3 +17T/C polymorphism is associated with a susceptibility to RA in Western Mexico. In addition, increased sCD28 levels are related to T/T genotype in RA patients. Show more
Keywords: CD28, IVS3 +17T/C, polymorphism, rheumatoid arthritis, sCD28
DOI: 10.3233/DMA-2011-0760
Citation: Disease Markers, vol. 30, no. 1, pp. 25-29, 2011
Authors: Bhushan, Bharat | Guleria, Randeep | Misra, Anoop | Luthra, Kalpana | Kumar, Guresh
Article Type: Research Article
Abstract: Background: Obstructive sleep apnea (OSA) is prevalent in 7.5% in urban Asian Indians. Peroxisome proliferator activated receptor gamma2 (PPARγ2) has been implicated in adipocyte differentiation. Neuropeptide Y (NPY) is also considered as a candidate gene for excess body fat accumulation. The association of PPARγ2 (Pro12Ala)} and NPY (Leu7Pro) gene polymorphisms with OSA has not been studied in Asian Indians. Objective: To study the distribution of PPARγ2 (Pro12Ala) and NPY (Leu7Pro) polymorphism in Asian Indians …with and without OSA. Methods and results: This study was carried out in 252 obese subjects [(body mass index (BMI > 25 kg/m^{2}) ]; 142 with OSA and 110 without OSA. Measurements included anthropometric and biochemical parameters (fasting blood glucose, lipid profile, various circumferences and skin-fold thicknesses). PPARγ2 (Pro12Ala) and NPY (Leu7Pro) gene} polymorphisms were studied in all subjects. The frequency of the variant allele (Ala12) of PPARγ2 gene was significantly higher in subjects with OSA (14.4%) when compared with subjects without OSA (5.5%; χ^{2} = 9.7; p = 0.001). The distribution of the variant allele (Pro7) of NPY gene was comparable in subjects with OSA (3.5%) and without OSA (3.6%; χ ^{2} = 0.001, p = 0.94). Conclusion: This study reveals a significantly higher frequency of PPARγ2 (Ala12) allele in obese Asian Indians with OSA when compared to obese Asian Indians without OSA. Show more
Keywords: Obstructive sleep apnea, PPAR gamma, neuropeptide Y, gene polymorphism, Asian Indians, obesity
DOI: 10.3233/DMA-2011-0762
Citation: Disease Markers, vol. 30, no. 1, pp. 31-38, 2011
Authors: Wilson, Nana O. | Jain, Vidhan | Roberts, Christina E. | Lucchi, Naomi | Joel, Pradeep K. | Singh, Mrigendra P. | Nagpal, Avinash C. | Dash, Aditya P. | Udhayakumar, Venkatachalam | Singh, Neeru | Stiles, Jonathan K.
Article Type: Research Article
Abstract: Plasmodium falciparum in a subset of patients can lead to a diffuse encephalopathy known as cerebral malaria (CM). Despite treatment, mortality caused by CM can be as high as 30% while 10% of survivors of the disease may experience short- and long-term neurological complications. The pathogenesis of CM involves alterations in cytokine and chemokine expression, local inflammation, vascular injury and repair processes. These diverse factors have limited the rate of discovery of prognostic predictors of fatal …CM. Identification of reliable early predictors of CM severity will enable clinicians to adjust this risk with appropriate management of CM. Recent studies revealed that elevated levels of CXCL10 expression in cerebrospinal fluid and peripheral blood plasma independently predicted severe and fatal CM. CXCR3, a promiscuous receptor of CXCL10, plays an important role in pathogenesis of mouse model of CM. In this study the role of corresponding CXCR3 ligands (CXCL11, CXCL10, CXCL9 & CXCL4) in fatal or severe CM was evaluated by comparing their levels in 16 healthy control (HC), 26 mild malaria (MM), 26 cerebral malaria survivors (CMS) and 12 non-survivors (CMNS) using enzyme linked immunosorbent assay (ELISA). Levels of CXCL4 and CXCL10 were significantly elevated in CMNS patients (p < 0.05) when compared with HC, MM and CMS. Elevated plasma levels of CXCL10 and CXCL4 were tightly associated with CM mortality. Receiver Operating Characteristic (ROC) curve analysis revealed that CXCL4 and CXCL10 can discriminate CMNS from MM (p < 0.0001) and CMS (p <0.0001) with an area under the curve (AUC)=1. These results suggest that CXCL4 and CXCL10 play a prominent role in pathogenesis of CM associated death and may be used as functional or surrogate biomarkers for predicting CM severity. Show more
Keywords: CXCL4, CXCL10, PF4, IP-10, malaria, cerebral malaria, Plasmodium falciparum, ROC curve
DOI: 10.3233/DMA-2011-0763
Citation: Disease Markers, vol. 30, no. 1, pp. 39-49, 2011
Authors: Hsieh, Kai-Sheng | Lai, Tsung-Jen | Hwang, Yu-Tung | Lin, Ming-Wei | Weng, Ken-Pen | Chiu, Yi-Ten | Ho, Tsyr-Yuh | Chen, Chi-Shan | Shiue, Yow-Ling | Hsiao, Michael | Tsai, Shih-Feng | Ger, Luo-Ping
Article Type: Research Article
Abstract: Kawasaki disease (KD) is the most common cause of pediatric acquired heart disease. KD patients have spontaneously high plasma/serum levels of IL-10 during the acute phase. Therefore, two independent studies were carried out to investigate the association between genetic variants in IL-10 promoter (−1082, −819, and −592) and risk of KD. A total of 134 trios were included for the family-based association study. A significantly preferential transmission of the C allele at loci −819 T > …C and −592 A > C for KD cases was observed (P_{permutation} = 0.029 and P_{permutation} = 0.034, respectively). There was a significant increase in the transmission of haplotype CC (p = 0.016) at the above two loci (OR, 1.632; 95% CI, 1.090–2.443; P_{permutation} = 0.019). We also carried out a follow-up case-control study that included 146 KD cases and 315 unrelated healthy children. {The haplotype CC (−819, −592) showed an increased risk of KD (but statistically non-significant; OR, 1.332; 95% CI, 0.987–1.797; p = 0.061). In diplotype analysis, a trend was found between number of CC haplotype and risk of KD (but non-significant, p =0.061). In conclusion, CC genotype and CC/CC diplotype at IL-10-819T > C and −592A > C were significantly associated with risk of KD in case-parent trio study, which were replicated partially in our follow-up case-control study. Show more
Keywords: Kawasaki disease, risk, IL-10, single-nucleotide polymorphisms, case-parent trio study, and case-control study
DOI: 10.3233/DMA-2011-0765
Citation: Disease Markers, vol. 30, no. 1, pp. 51-59, 2011
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