The present case-control study was carried out to investigate the association of polymorphism in cytochrome P450 2D6 (CYP2D6) and N-acteyltransferase-2 (NAT2), that are involved in the metabolism and detoxification of chemicals causing Parkinson disease (PD) like symptoms, with PD. Our data demonstrated increased frequency of CYP2D6&#x2a;2 (1749G/C and 2938C/T), CYP2D6&#x2a;4 (1934G/A) and CYP2D6&#x2a;10A (188C/T) polymorphisms in PD cases when compared to the controls. Statistical analysis revealed the significant association of CYP2D6&#x2a;4 (1934G/A) and CYP2D6&#x2a;10A (188C/T) polymorphism with PD. Likewise, increased frequency of NAT2&#x2a;7 polymorphism that leads to the slow acetylator phenotype was observed in PD patients with more than fivefold increased risk (OR: 5.55; 95&#x25;CI: 0.56&#x2013;54). No change was observed in the frequency of NAT&#x2a;5 or NAT&#x2a;6 alleles in the cases. Further, cases carrying combination of heterozygous genotypes of CYP2D6&#x2a;4 or CYP2D6&#x2a;10A(188C &#x3e; T) and NAT2&#x2a;5 were found to be at significantly higher risk for PD demonstrating the importance of gene-gene interactions in determining susceptibility to PD.

Madhu Singh

Vinay K. Khanna

Rakesh Shukla

Devendra Parmar

Association of Polymorphism in Cytochrome P450 2D6 and N-Acetyltransferase-2 with Parkinson&#x2019;s Disease

Background: The development of cardiovascular disease in ESRD patients is considered to be associated with oxidative stress. NAD(P)H oxidase has attracted attention as mechanisms of generating oxidative stress. We investigated the relation between the genotype of the C242T CYBA polymorphism of the NADPH oxidase and the development of cardiovascular disease in ESRD patients.Methods: A total of 289 ESRD patients were recruited and allocated to one of the two groups: patients without cardiovascular disease (group N; n=192) and patients developing cardiovascular disease (group D; n=97). The C242T CYBA polymorphism was determined by RFLP-PCR methods.Results: The frequency of the C242T CT+TT genotype was significantly lower in group D than in group N (9.1 vs. 20.2&#x25;). In multiple Logistic regression analysis, systolic blood pressure, smoking history and this gene polymorphism were shown to be independent variables for the development of cardiovascular disease in ESRD patients.Conclusions: These results suggest that assessment of the C242T CYBA polymorphism of the NADPH oxidase may be useful in identifying the risk for developing cardiovascular disease in ESRD patients.

Feng-Ying Tang

Ying Zhu

Gui Hua Wang

Xiong-Wei Xie

Relation between Development of Cardiovascular Disease and the C242T CYBA Polymorphism of the NADPH Oxidase in ESRD Patients

Background: Micro-RNAs (miRNAs) regulate one-third of all protein-coding genes and are fundamental in the pathophysiology of a wide range of diseases. We studied the expression of several miRNA species (miR-200 family, miR-205 and miR-192) in the urinary sediment of patients with IgA nephropathy (IgAN).Methods: We studied 43 patients with biopsy-proven IgAN. Urinary expression of miRNAs was determined and compared to that from 13 healthy controls.Results: The levels of urinary miR-200a, miR-200b and miR-429, but not miR-200c, miR-141, miR-205, or miR-192, were down-regulated in patients with IgAN. Proteinuria significantly correlated with urinary expression of miR-200a (r = &#x2212;0.483, P &lt; 0.001), miR-200b (r = &#x2212;0.448, P = 0.001) and miR-429 (r = &#x2212;0.466, P = 0.001). Baseline renal function significantly correlated with urinary expression of miR-200b (r = 0.512, P &lt; 0.001) and miR-429 (r = 0.425, P = 0.005). Urinary gene expression of ZEB2 inversely correlated with miR-200b (r = &#x2212;0.321, P = 0.017); and vimentin expression inversely correlated with that of miR-200a (r = &#x2212;0.360, P = 0.007), miR-200b (r = &#x2212;0.416, P = 0.002) and miR-429 (r = &#x2212;0.375, P = 0.005). After 33.4 ± 12.6 months, the rate of renal function decline significantly correlated with urinary expression of miR-200b (r = 0.316, P = 0.034).Conclusions: Urinary expression of miR-200a, miR-200b and miR-429 were down-regulated in patients with IgAN, and the degree of reduction correlated with disease severity and rate of progression. The results suggested that these miRNA species might play important roles in the pathophysiology of IgAN. Further studies are needed to clarify the role of urinary miRNA repression as a non-invasive marker of IgAN.

Gang Wang

Bonnie Ching-Ha Kwan

Fernand Mac-Moune Lai

Kai-Ming Chow

Philip Kam-Tao Li

Cheuk-Chun Szeto

Expression of MicroRNAs in the Urinary Sediment of Patients with IgA Nephropathy

Although polymorphisms in glutathione S-transferase (GST) have been associated with the risk of bladder cancer (BC), few reports provide information about the development of BC. The aim of the present study was to investigate the effect of homozygous glutathione S-transferase-&#x3bc; (GSTM1) and glutathione S-transferase-&#x26;phis; (GSTT1) deletions as prognostic markers in non-muscle-invasive bladder cancer (NMIBC). A total of 241 patients with primary NMIBC were enrolled in this study. GSTM1 and GSTT1 polymorphisms were analyzed by multiplex polymerase chain reaction (PCR) using blood genomic DNA. The results were compared with clinicopathological parameters. The prognostic significance of the GSTs was evaluated by Kaplan-Meier and multivariate Cox regression model. A statistically significant association between genotype and histopathological parameter was not observed. The patients with the GSTT1-positive genotype had significantly reduced recurrence- and progression-free survival than those with the GSTT1-null genotype (log-rank test, p &#60; 0.05, respectively). Recurrenceand progressionfree survival were not related to the GSTM1 genotypes. In multivariate regression analysis, the GSTT1positive genotype was the independent predictor for recurrence [hazard ratio (HR), 1.631; p = 0.043] and progression (HR, 3.418; p = 0.006). These results suggested that the GSTT1 genotype could be a useful prognostic marker for recurrence and progression in NMIBC.

Yun-Sok Ha

Chunri Yan

Min Su Lym

Pildu Jeong

Won Tae Kim

Yong-June Kim

Seok-Joong Yun

Sang-Cheol Lee

Sung-Kwon Moon

Yung Hyun Choi

Wun-Jae Kim

GSTT1 as a Prognosticator for Recurrence and Progression in Patients with Non-Muscle-Invasive Bladder Cancer

The exact molecular background and the connection between protein and mRNA expression in colorectal cancer (CRC) development and progression are not completely elucidated. Our purposes were the identification of protein markers of colorectal carcinogenesis and progression using protein arrays and validation on tissue microarrays. The connection between antibody and mRNA expression array results was also examined. Using cancerous and adjacent normal samples from 10 patients with early and 6 with advanced CRC, 67 differentially expressed genes were identified between normal and cancerous samples. A marker set containing 6 proteins (CCNA1, AR, TOP1, TGFB, HSP60, ERK1) was developed which could differentiate normal specimen, early and late stage CRC with high sensitivity and specificity. Dukes D stage samples were analyzed on HGU133plus2.0 microarrays. In these samples, mRNA and protein expression of 143 genes showed strong positive correlations (R2 &#x3e; 0.8), while a negative correlation (R2 &#x3e; 0.9) was found in case of 95 genes. Based on our results a correlation could be established between transcriptome and antibody array results, hence the former may be used as a high-capacity screening method before applying antibody arrays containing already planned targets. Antibody microarrays may have a fundamental importance in testing of marker combinations and future application in diagnostics of tumorous diseases.

S&#xe1;ndor Spis&#xe1;k

Barnab&#xe1;s Galamb

Ferenc Sipos

Orsolya Galamb

Barnab&#xe1;s Wichmann

Norbert Solymosi

Bal&#xe1;zs Nemes

Jeannette Moln&#xe1;r

Zsolt Tulassay

B&#xe9;la Moln&#xe1;r

Applicability of Antibody and mRNA Expression Microarrays for Identifying Diagnostic and Progression Markers of Early and Late Stage Colorectal Cancer

Bronchopulmonary dysplasia (BPD) is the chronic lung disease of preterm infants and still represents a major burden of prematurity. Several clinical risk factors for the onset of the disease are already known. In addition, some candidate genes have recently been identified. We set out to determine clinical as well as genetic risk factors for the development of BPD in the German population.155 infants born with a gestational age &#2264; 28 at the tertiary neonatal Centre, Freiburg, were recruited. Clinical data were recorded from hospital charts. 47 children developed moderate or severe BPD. For genetic analyses, 37 polymorphisms within sixteen genes were genotyped on all children.The strongest epidemiological risk factor for BPD was birth weight, followed by low gestational age. Genetic association was detected with single polymorphisms within Tumour necrosis factor alpha, Toll like receptor 10 and vascular endothelial growth factor. The former two genes showed also association with BPD in haplotype analyses. In conclusion, association of BPD was far more convincingly found with a few clinical factors than with genetic polymorphisms. This underscores the genetic complexity of the disease. Furthermore, the identification of predisposing genetic polymorphisms might be hampered by the complex interaction between clinical and genetic factors.

Beena Mailaparambil

Marcus Krueger

Ulrike Heizmann

Katharina Schlegel

Jessica Heinze

Andrea Heinzmann

Genetic and Epidemiological Risk Factors in the Development of Bronchopulmonary Dysplasia

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Disease Markers publishes papers related to the identification of disease markers, the elucidation of their role and mechanism, as well as their application in the prognosis, diagnosis and treatment of diseases.

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Chief Editor Paola Gazzaniga is an Associate Professor in the Department of Molecular Medicine at Sapienza University of Rome, Italy. Her core research focuses on liquid biopsies in patients with solid tumors.

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Disease Markers publishes papers related to the identification of disease markers, the elucidation of their role and mechanism, as well as their application in the prognosis, diagnosis and treatment of diseases.

Disease Markers