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Authors: Govindan, Sujatha | Shaik, Noor Ahmad | Vedicherla, Bhavani | Kodati, Vijayalakshmi | Rao, Kaipa Prabhakar | Hasan, Qurratulain
Article Type: Research Article
Abstract: Endometriosis and fibroids are estrogen-dependent benign pathologies of the uterus, which account for infertility and pelvic pain along with dysmenorrhea in women. Suppression of the disease and recurrence after discontinuing hormone therapy strongly suggests that these are responsive to hormones, especially estrogen, which acts via its receptor. A T/C SNP in intron 1 and exon 2 boundary of estrogen receptor (ER) α gene recognized by PvuII enzyme has been associated with several female pathologies like breast …cancer, osteoporosis, endometriosis and fibroids in various ethnic groups. The aim of the present study was to assess this ER α T/C polymorphism in endometriosis and fibroid patients from Asian Indian population. Genomic DNA was isolated from 367 women, who included 110 cases of endometriosis, 142 cases of uterine fibroids and 115 healthy age matched women volunteers. PCR was carried out to amplify ER α gene followed by restriction digestion with Pvu II. Results indicate a significant association of C allele with both endometriosis [OR=2.6667, 95% CI=1.4166 to 5.0199; p < 0.05] and fibroids [2.0833, 95% CI=1.1327 to 3.8319; p < 0.05]. Further studies are needed in larger population to establish ERα C allele as a risk marker for endometriosis and fibroids in Asian Indian women. Ethnicity, race, diet etc may play a role in susceptibility to endometriosis and fibroids and further studies are warranted in this area. Show more
Keywords: Estrogen receptor, Pvu II polymorphism, Intron 1, endometriosis, fibroids
DOI: 10.3233/DMA-2009-0625
Citation: Disease Markers, vol. 26, no. 4, pp. 149-154, 2009
Authors: Fintelman-Rodrigues, N. | Corrêa, J.C. | Santos, J.M. | Pimentel, M.M.G. | Santos-Rebouças, C.B.
Article Type: Research Article
Abstract: Recent evidence shows that almost 92% of the DS children are born from young mothers, suggesting that other risk factors than advanced maternal age must be involved. In this context, some studies demonstrated a possible link between DS and maternal polymorphisms in genes involved in folate metabolism. These polymorphisms, as well as low intake of folate could generate genomic instability, DNA hypomethylation and abnormal segregation, leading to trisomy 21. We compared the frequency of CBS 844ins68, …MTR 2756A>G, RFC-1 80G> A and TC 776C>G polymorphisms among 114 case mothers and 110 matched controls, in order to observe whether these variants act as risk factors for DS. The genotype distributions revealed that there were not significant differences between both samples. However, when we proceed the multiplicative interaction analyses between the four polymorphisms described above together with the previously studied MTHFR 677C>T, MTHFR 1298A>C and MTRR 66A>G polymorphisms, our results show that the combined genotype TC 776CC / MTHFR 677TT and TC 776CC / MTR 2756AG were significantly higher in the control sample. Nevertheless, there was no significant association after Bonferroni correction. Our results suggest that maternal folate-related polymorphisms studied here have no influence on trisomy 21 susceptibility in subjects of Brazilian population. Show more
Keywords: Down syndrome, folate, polymorphisms, TC
DOI: 10.3233/DMA-2009-0626
Citation: Disease Markers, vol. 26, no. 4, pp. 155-161, 2009
Authors: Samy, Nervana | Hashim, Maha | Sayed, Magda | Said, Mohamed
Article Type: Research Article
Abstract: Background: Women with polycystic ovary syndrome (PCOS) have an increased prevalence of insulin resistance (IR) and related disorders. Elevated serum levels of high sensitivity CRP (hs-CRP), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) reflect low-grade chronic inflammation and have been associated with several insulin-resistant states; they are useful cardiovascular risk markers. The objective of this study was to investigate whether soluble inflammatory markers are altered in PCOS focusing on its relationship …with obesity and indexes of insulin resistance. Patients and methods: One hundred and eight women with PCOS and 75 healthy women were recruited. Patients were divided according to body mass index (BMI) into two groups; group I (BMI < 27 kg/m^{2} ) and group II (BMI ⩾ 27 Kg/m^{2} ). Serum levels of hs-CRP, IL-6, and TNF-α, lipid and hormone profiles were measured. Results: PCOS patients had increased levels of testosterone, luteinizing hormone (LH), androstendione, insulin level and HOMA index compared to healthy BMI matched controls. High-density lipoprotein (HDL) concentrations were significantly reduced in both patient groups compared to their controls, while triglyceride levels were significantly increased in obese group compared to controls. There were no significant difference in serum inflammatory markers hs-CRP, IL-6 and TNF-α between group I and their matched controls. On the other hand, there were significant increase in these markers between group II and their matched controls. There were highly significant positive correlation between hs-CRP and IL-6 (r=0.702, P< 0.001) and between hs-CRP and TNF-α (r=0.621, P<0.001), also between IL-6 and TNF-α (r=0.543, P< 0.001). These inflammatory markers correlated significantly with BMI and HOMA index. Multiple regression analysis revealed that BMI and HOMA were predictors of IL-6 levels (b=11.173, P< 0.001, b=13.564, P< 0.001 respectively) and BMI was the only predictor of hs-CRP levels (b=12.578, P< 0.001) and TNF-α levels (b=0.134, P<0.001). Conclusion: PCOS and obesity induce an increase in serum inflammatory cardiovascular risk markers. The precise mechanisms underlying these associations require additional studies to clarify the state of the cardiovascular system in women with PCOS compared with controls in large numbers of patients to determine the relative contribution of different factors including insulin resistance, androgen status and BMI. Show more
Keywords: Polycystic ovary syndrome, inflammatory markers, insulin resistance, BMI
DOI: 10.3233/DMA-2009-0627
Citation: Disease Markers, vol. 26, no. 4, pp. 163-170, 2009
Authors: Todorović-Raković, N. | Nešković-Konstantinović, Z. | Nikolić-Vukosavljević, D.
Article Type: Research Article
Abstract: The aim of this study was to determine the relationship between amplification of HER2 (Human epidermal growth factor receptor 2) and Topo2a (topoisomerase 2a) and their influence on prognosis in metastatic breast cancer (MBC) patients. Amplification of both HER2 and Topo2a genes was determined by chromogenic in situ hybridization (CISH) in primary tumor tissue of 71 MBC patients. Starting point for follow-up was the time of diagnosis of metastatic disease. Although there …was significant correlation between HER2 amplification and Topo2a alterations, Topo2a amplification was not strictly related to HER2 amplification. Follow-up of patients showed that there was no difference in MBC survival between HER2-nonamplified and HER2-amplified patients for subgroup as whole, but there was significant difference in MBC survival between patients with and without Topo2a amplification. HER2 amplification showed prognostic value in subgroups of patients, as well as Topo2a. Combination of these two genes with different status (nonamplified, amplified, coamplified) indicated that they might have additive effect. Also, it has been shown that Topo2a-amplified cases have poorer survival than Topo2a-nonamplified, when treated with CMF therapy. Topo2a amplification seems to be more promising biomarker of MBC survival, than HER2, and potential marker of resistance to CMF therapy. Show more
Keywords: Metastatic breast cancer, CISH, HER2, Topo2a
DOI: 10.3233/DMA-2009-0628
Citation: Disease Markers, vol. 26, no. 4, pp. 171-180, 2009
Authors: Golledge, Alexandra L.V. | Walker, Philip | Norman, Paul E. | Golledge, Jonathan
Article Type: Research Article
Abstract: Objectives: Inflammation is critical in abdominal aortic aneurysm (AAA) but there is no current consensus on which inflammation related cytokines are important. The aim of this review was to systemically assess previous studies investigating the relative expression of inflammation associated cytokines within human AAA samples. Methods: The MEDLINE database was searched for studies which simultaneously examined an array of different inflammation associated cytokines in aortic samples in order to identify those …associated with AAA. Focused searches were then conducted for further studies assessing relative concentrations of these cytokines in aortic samples in relation to AAA. Appropriate studies were assessed by two reviewers independently. Results: Eighteen studies were included. A number of different cytokines have been consistently found to be upregulated within AAA by comparison to aortic samples removed from patients without cardiovascular disease, however findings relative to samples of aortic athero-thrombosis were less consistent. TNFA and INFG appear to be the most consistently associated with AAA in studies using both normal and atherosclerotic controls. Cautious interpretation of these data is recommended due to a number of methodological problems. Conclusions: This systematic review suggests that TNFA and INFG are the most consistently upregulated cytokines in large AAAs. Further studies utilizing larger populations, new proteomic techniques and better patient matching are required. Show more
DOI: 10.3233/DMA-2009-0629
Citation: Disease Markers, vol. 26, no. 4, pp. 181-188, 2009
Authors: Rodríguez-Yáñez, Manuel | Sobrino, Tomás | Blanco, Miguel | de la Ossa, Natalia Pérez | Brea, David | Rodríguez-González, Raquel | Leira, Rogelio | Dávalos, Antonio | Castillo, José
Article Type: Research Article
Abstract: Background: Stroke subtype diagnosis leads to specific therapies to reduce recurrences. Because nearly one third of patients remain with unknown etiology after a complete screening workup, we aim to investigate whether molecular markers of myocardial damage were associated with cardioembolic stroke and if they were useful to reclassify strokes of undetermined etiology. Methods: We included 262 patients with first ischemic stroke within the first 12 hours. Stroke subtype was evaluated by TOAST criteria. Stroke of …undetermined origin were reclassified into likely atherothrombotic or likely cardioembolic according to a predefined non-validated algorithm. Blood samples were obtained on admission to determine serum levels of molecular markers (pro-BNP, pro-ANP and CK-MB) of myocardial damage. Results: Patients with cardioembolic infarct showed higher levels of pro-BNP, pro-ANP and CK-MB. Pro-BNP > 360 pg/mL was independently associated with cardioembolic stroke (OR: 28.51, CI95%: 5.90–136.75, p< 0.0001). Stroke etiology was undetermined in 82 patients (31%); 34 were reclassified as likely cardioembolic, 22 as likely atherothrombotic, and 26 remained as undetermined. Pro-BNP > 360 pg/mL was the only factor independently associated with likely cardioembolic stroke. Conclusions: Pro-BNP levels higher than 360 pg/mL are associated with cardioembolic stroke and may be useful to reclassify undetermined strokes as of cardioembolic origin. Show more
Keywords: Brain natriuretic peptide, cardioembolic stroke, ischemic stroke, ischemic stroke classification
DOI: 10.3233/DMA-2009-0630
Citation: Disease Markers, vol. 26, no. 4, pp. 189-195, 2009
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