Disease Markers - Volume 27, issue 5

Authors: Signorello, Lisa B. | Cai, Qiuyin | Tarone, Robert E. | McLaughlin, Joseph K. | Blot, William J.

Article Type: Research Article

Abstract: The purpose of this study was to estimate black/white differences in cotinine levels for current smokers of both sexes, and to explore the potential contribution of mentholated cigarettes to these differences. Sera from 255 current smokers sampled from Southern Community Cohort Study participants (65 black men, 65 black women, 63 white men, 62 white women) were analyzed for cotinine, and linear regression was used to model the effect of race on cotinine level, adjusting for the …number of cigarettes smoked within the last 24 hours, use of menthol vs. non-menthol cigarettes, exposure to environmental tobacco smoke, and age. Black smokers smoked fewer cigarettes than white smokers, yet had crude mean cotinine levels nearly as high or higher than white smokers. After multivariate adjustment, cotinine levels were an average of 50 ng/ml higher among black than white women (p=0.008) and non-significantly 12 ng/ml higher among black than white men (p=0.52). We observed no increase in cotinine levels associated with menthol cigarette use. We conclude that differences in cotinine levels among smokers suggest racial variation in exposure to and/or metabolism of tobacco smoke constituents, but our findings do not support a role for menthol preference in this disparity. Show more

Keywords: Cotinine, smoking, metabolism, lung cancer, race, African Americans

DOI: 10.3233/DMA-2009-0661

Citation: Disease Markers, vol. 27, no. 5, pp. 187-192, 2009

Authors: Lin, Z. | Poritz, L. | Franke, A. | Li, T.Y. | Ruether, A. | Byrnes, K.A. | Wang, Y. | Gebhard, A.W. | MacNeill, C. | Thomas, N.J. | R. Wu, | Schreiber, S. | Koltun, W.A.

Article Type: Research Article

Abstract: Background: The association of DLG5 R30Q with IBD has been replicated in several populations, but is not statistically significant in others. We studied the incidence of DLG5 alleles in a population of IBD patients from Pennsylvania. Methods: DLG5 R30Q (rs1248696) and G1066G (rs1248634) were analyzed with PCR-based RFLP methods in a total of 521 subjects, that included 105 individuals with IBD and 139 without IBD from a familial IBD registry, 107 with sporadic IBD, …and 170 unrelated healthy controls. R30Q was further analyzed with SNPlex™ Genotyping System in 473 samples. Results: RFLP genotyping data showed that, DLG5 R30Q was significantly associated with IBD overall (p=0.006), and separately with CD (p=0.009) and UC (p=0.024). The association of R30Q with IBD was entirely due to a male-associated effect (male vs female p=0.015 vs 0.241 (IBD), p=0.024 vs 0.190 (CD), and p=0.019 vs 0.575 (UC)). The frequency of the A allele carriage was elevated in both affected and unaffected members in the familial IBD cohort compared to healthy controls (p=0.037). In the family pedigrees, we observed differences in the expression of IBD in individuals carrying the A allele between families. Conclusions: In the studied population, DLG5 R30Q was associated with all forms of IBD. An elevated presence of the R30Q variant was observed in all members of a familial IBD registry. This association of the R30Q variant with IBD was male-specific. Show more

Keywords: DLG5 R30Q, familial IBD registry, genetic association, inflammatory bowel disease, male-specific

DOI: 10.3233/DMA-2009-0662

Citation: Disease Markers, vol. 27, no. 5, pp. 193-201, 2009

Authors: Yadav, Sharawan | Singhal, Naveen Kumar | Singh, Virendra | Rastogi, Neeraj | Srivastava, Pramod Kumar | Singh, Mahendra Pratap

Article Type: Research Article

Abstract: Cytochrome P450 1B1 (CYP1B1) and catechol-$O$-methyltransferase (COMT) enzymes play critical roles in estrogen metabolism. Alterations in the catalytic activity of CYP1B1 and COMT enzymes have been found associated with altered breast cancer risk in postmenopausal women in many populations. The substitution of leucine (Leu) to valine (Val) at codon 432 increases the catalytic activity of CYP1B1, however, substitution of Val to methionine (Met) at codon 158 decreases the catalytic activity of COMT. The present study was …performed to evaluate the associations of CYP1B1 Leu^{432} Val and/or COMT Val^{158} Met polymorphisms with total, premenopausal and postmenopausal breast cancer risks in Indian women. COMT and CYP1B1 polymorphisms in controls and breast cancer patients were analyzed employing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) followed by gel electrophoresis. Although CYP1B1 and COMT genotypes did not exhibit statistically significant association with breast cancer risks when analyzed individually, COMT wild type (Val^{158} Val) in combination with CYP1B1 heterozygous variant (Leu^{432} Val) [OR: 0.21; 95% CI (0.05–0.82), p value; 0.021] and COMT heterozygous variant (Val^{158} Met) in combination with CYP1B1 wild type (Leu^{432} Leu) [OR: 0.29; 95% CI (0.08–0.96), p value; 0.042] showed significant protective association with premenopausal breast cancer risk. The results demonstrate that CYP1B1 wild type in combination with COMT heterozygous or their inverse combination offer protection against breast cancer in premenopausal Indian women. Show more

Keywords: Breast cancer, genetic polymorphism, CYP1B1, COMT

DOI: 10.3233/DMA-2009-0663

Citation: Disease Markers, vol. 27, no. 5, pp. 203-210, 2009

Authors: Jin, Zhao | Luxiang, Chi | Huadong, Zhou | Yanjiang, Wang | Zhiqiang, Xu | Hongyuan, Cao | Lihua, Huang | Xu, Yi

Article Type: Research Article

Abstract: Endothelin converting enzyme (ECE-1) is a candidate Alzheimer disease susceptibility gene. It was previously reported that western individuals homozygous for the C-338A polymorphism (AA) within the ECE1 gene promoter region are at reduced risk of developing late onset Alzheimer disease (LOAD). A further polymorphism, T-839G, is present within the ECE1 promoter region but a potential association with LOAD has not been studied. We therefore studied possible associations between these ECE1 polymorphisms …and LOAD in a Chinese population. Subjects comprised 376 Chinese LOAD patients and 376 age- and sex-matched controls; all subjects were typed for the ECE1 C-338A and the T-839G polymorphisms. We report that the frequency of the 338A allele was decreased in LOAD patients compared to controls (adjusted OR =0.73; 95% CI=0.54–0.98; P=0.03). There was no significant association between T-839G genotype and LOAD, however the combined 839T/338A haplotype was significantly associated with decreased risk of LOAD (OR=0.73; 95% CI=0.57–0.93; P=0.01). This study argues that the ECE1 338A allele is protective against LOAD in a Chinese population. Show more

Keywords: Alzheimer's disease, polymorphism, ECE-1

DOI: 10.3233/DMA-2009-0665

Citation: Disease Markers, vol. 27, no. 5, pp. 211-215, 2009

Authors: Menegatti, Elisa | Davit, Annalisa | Francica, Simona | Berardi, Daniela | Rossi, Daniela | Baldovino, Simone | Tovo, Pier Angelo | Sena, Luigi M. | Roccatello, Dario

Article Type: Research Article

Abstract: Immune and inflammatory response activation is a common feature of connective tissue diseases and systemic vasculitis. The aim of our study was to evaluate the possible involvement of TNFα c.-308A > G, IL-10 c.-1082A > G, uteroglobin c.38A > G, TGFβ 1 c.869C > T and NFκB2 c.-1837T > C gene polymorphisms in susceptibility to connective tissue diseases. Our study cohort included 68 unrelated patients affected by rheumatoid arthritis (RA) (37 patients) and ANCA-positive …[micropolyangiitis (mPA) 17 patients] or ANCA-negative systemic vasculitis [including 8 patients with Henoch-Schönlein purpura (HSP) and 6 patients with mixed cryoglobulinaemia (MC)] as well as 98 control subjects. Allele frequency analysis of uteroglobin c.38G > A polymorphism showed a significant increase in the c.38A allele in patients (p= 0.002). Genotype frequency analysis of uteroglobin and NF-κB2 gene polymorphisms in patients showed an increase in c.38GA and c.38AA genotypes in the uteroglobin gene (p=0.02) coupled with an increase in homozygous c.-1837CC in the NF-κB2 gene (p=0.02). Our data suggest that genetic variation in UG and NF-κB2 pathways could have effects in connective tissue disease susceptibility. Show more

Keywords: Connective diseases, systemic vasculitis, uteroglobin, polymorphisms

DOI: 10.3233/DMA-2009-0666

Citation: Disease Markers, vol. 27, no. 5, pp. 217-223, 2009

Authors: Gallegos-Arreola, M.P. | Figuera, L.E. | Ortiz, G.G. | Jiménez-Gil, F.J. | Ramírez-Vega, J. | Ruíz-Sandoval, J.L. | Puebla-Pérez, A.M. | Troyo-Sanroman, R. | García-Ortiz, J.E. | Sanchez-Corona, J. | Zúñiga-González, G.M.

Article Type: Research Article

Abstract: Background: The association of the apolipoprotein (Apo E) -epsilon4 allele to neurodegenerative diseases such as Parkinson's disease (PD) has been analyzed in several studies. This association has been identified by amyloid deposits and neurofibrillary tangles in the brains of patients with neurodegenerative diseases. Method: In this study the possible relationship between Apo E alleles and PD patients was analyzed in 105 patients with PD and 107 healthy controls from a Mexican population. …Results: Allele analysis in PD vs. controls was: ε2 in 6% and 2.3%, respectively; ε3 in 73% and 88.3%; and ε4} in 21% and 9.4%. The ε3 allele showed a protective risk effect with an Odds ratio (OR) of 0.36 (95%CI 0.20–0.61) and p < 0.05; contrary results were observed for the ε4 allele, which showed an increased risk for PD, with an OR of 2.57(95% CI 1.42–4.79) and p < 0.05. Upon multivariate analysis showed PD risk was evident in patients who were carriers of the genotype ε3/ε4; age group (fifty or more years) and had exposure to pesticides and solvents (p < 0.05). Conclusions: The ε3/ε3}; ε3/ε4 genotypes of the Apo E, were positively associated with sporadic PD. Show more

DOI: 10.3233/DMA-2009-0667

Citation: Disease Markers, vol. 27, no. 5, pp. 225-230, 2009

Authors: Ashavaid, T.F. | Raghavan, Rani | Shah, Swarup | Kapadia, Asha | Almel, Sachin | Desai, Devendra

Article Type: Research Article

Abstract: Introduction: Development of DNA-based tests for TPMT/DPD polymorphisms can help clinicians and patients to make important decisions about cancer treatment. Also, due to lack of Indian data, we aimed at the development and validation of these tests in Indian patients. Materials and Methods: Molecular assays were used for identifying TPMT/DPD variations; validated by DNA sequencing. Results: Molecular assays have been used for screening TPMT*2, *3A, *3B, *3C alleles and IVS14+1(G→A) in DPD gene. A …patient, exhibiting neutropenia on 6-MP was observed to be G460A-homozygote, while, two Acute Lymphoblastic Leukemia (ALL) patients with side-effects exhibited wild-type alleles. Two patients showing 6-MP side-effects and responding well to the same drug at later stage also carried wild-type alleles. Discussion: G460A homozygosity in a patient allowed clinicians to stop 6-MP treatment, improving patient's health status. Two ALL patients showing side-effects were wild-type, indicating presence of unidentified rare variations. Two patients with wild-type allele showed side-effects during 6-MP treatment, but responded well to same drug at later stage, suggesting side-effects to be attributable to multiple biological and environmental processes. Absence of IVS14+1(G→A) in DPD gene will not exclude possibility of another mutation. Conclusion: Molecular assays for determining common TPMT/DPD variations, can provide accurate diagnosis and efficient therapies in future clinical studies. Show more

Keywords: Chemotherapy, cancer, genetic tests, SNP's, A719G, G460A, G238C, IVS14+1(G→A), acute lymphoblastic leukemia (ALL), azathioprine, pharmacogenomics, PCR, toxicity, diagnosis

DOI: 10.3233/DMA-2009-0668

Citation: Disease Markers, vol. 27, no. 5, pp. 231-238, 2009

Authors: Satoh, Jun-ichi | Tabunoki, Hiroko | Arima, Kunimasa

Article Type: Research Article

Abstract: The pathogenesis of Alzheimer disease (AD) involves the complex interaction between genetic and environmental factors affecting multiple cellular pathways. Recent advances in systems biology provide a system-level understanding of AD by elucidating the genome-wide molecular interactions. By using KeyMolnet, a bioinformatics tool for analyzing molecular interactions on the curated knowledgebase, we characterized molecular network of 2,883 all stages of AD-related genes (ADGs) and 559 incipient AD-related genes (IADGs) identified by global gene …expression profiling of the hippocampal CA1 region of AD brains in terms of significant clinical and pathological correlations (Blalock et al., Proc Natl Acad Sci USA 101: 2173-2178, 2004). By the common upstream search, KeyMolnet identified cAMP-response element-binding protein (CREB) as the principal transcription factor exhibiting the most significant relevance to molecular networks of both ADGs and IADGs. The CREB-regulated transcriptional network included upregulated and downregulated sets of ADGs and IADGs, suggesting an involvement of generalized deregulation of the CREB signaling pathway in the pathophysiology of AD, beginning at the early stage of the disease. To verify the in silico observations in vivo, we conducted immunohistochemical studies of 11 AD and 13 age-matched control brains by using anti-phoshorylated CREB (pCREB) antibody. An abnormal accumulation of pCREB imunoreactivity was identified in granules of granulovacuolar degeneration (GVD) in the hippocampal neurons of AD brains. These observations suggest that aberrant CREB-mediated gene regulation serves as a molecular biomarker of AD-related pathological processes, and support the hypothesis that sequestration of pCREB in GVD granules is in part responsible for deregulation of CREB-mediated gene expression in AD hippocampus. Show more

Keywords: Alzheimer disease, CREB, granulovacuolar degeneration, keymolnet, molecular network, systems biology

DOI: 10.3233/DMA-2009-0670

Citation: Disease Markers, vol. 27, no. 5, pp. 239-252, 2009

Article Type: Other

Abstract: The online version of the original article can be found at: http://www.iospress.metapress.com/content/ 2266v526t7245187/

DOI: 10.3233/DMA-2009-0686

Citation: Disease Markers, vol. 27, no. 5, pp. 253-253, 2009