Disease Markers - Volume 21, issue 1

Article Type: Other

Citation: Disease Markers, vol. 21, no. 1, pp. 1-2, 2005

Authors: Zhou, Xiao Feng | Cui, Jing | DeStefano, Anita L. | Chazaro, Irmarie | Farrer, Lindsay A. | Manolis, Athanasios J. | Gavras, Haralambos | Baldwin, Clinton T.

Article Type: Research Article

Abstract: Genetic variations that predispose individuals to complex disorders, such as essential hypertension, may be found in gene coding regions, intronic regions or in gene promoter regions. Most studies have focused on gene variations that result in amino acid substitutions because they result in different isoforms of the protein, presumably resulting in differences in protein properties. Less attention has been placed on the role of intronic or promoter mutations. In this report, we examined two single nucleotide …polymorphisms (SNPs) in the catalase (CAT) gene prompter region in a cohort of hypertensive Caucasians and African Americans with a Mass Spec based Homogenous MassEXTEND assay. We found an association when a specific combination of the two promoter SNPs was examined in Caucasians. No association was observed in African Americans. Our data suggest that genetic variations in the promoter region of catalase gene influence the susceptibility to essential hypertension. In addition, the genetic factors that contribute to hypertension maybe different between ethnic groups. Show more

Keywords: catalase, essential hypertension, SNP, promoter

Citation: Disease Markers, vol. 21, no. 1, pp. 3-7, 2005

Authors: Klintschar, Michael | Immel, Uta-Dorothee | Stiller, Dankwart | Kleiber, Manfred

Article Type: Research Article

Abstract: TH01 is a tetrameric short tandem repeat locus located in intron 01 of the tyrosine hydroxylase gene. The tyrosine hydroxylase catalyzes the hydroxylation of L-tyrosine to L-DOPA and is the rate limiting enzyme in the synthesis of catecholamines like noradrenaline or adrenaline, which are pivotal in the regulation of blood pressure. In a clinical study a strong correlation between alleles *9.3 and *10 and essential hypertension was observed ([2] Hypertension 32: 676–682). To further investigate this …association, we typed TH01 in 296 autopsy cases and correlated the genotypes to the heart weight as parameter for myocardial hypertrophy. No significant correlation was observed. Moreover, dividing the studied cases into 2 groups, one including 172 casualties from hypertension-associated diseases (myocardial infarction, left heart failure, aortic aneurysm, spontaneous intracerebral bleeding and cerebral infarction) and one consisting of 124 cases of death unrelated to hypertension, revealed similar allelic frequencies for both groups. Our data thus suggest that TH01 long alleles appear not to lead to a significant increase in the incidence of myocardial hypertrophy or other hypertension associated diseases. This could be explained by a relatively small impact of the TH01 genotype on the blood pressure or by counteraction of another mechanism related to catecholamines and their effect on the human body. Show more

Citation: Disease Markers, vol. 21, no. 1, pp. 9-13, 2005

Authors: Fernández-Mestre, M.T. | Yehirobi, Castro | Montagnani, S. | Balbas, O. | Layrisse, Z.

Article Type: Research Article

Abstract: The genetic variation at the Apolipoprotein E locus (APOE) is an important determinant of plasma lipids and has been implicated in various human pathological conditions. The objective of the present study was to estimate the distribution of APOE alleles in five Venezuelan communities: two Amerindian tribes (Bari and Yucpa), one Negroid population from Curiepe, one Caucasoid population from Colonia Tovar and the mestizo urban population living in Caracas. The APOE*3 allele was the most common allele …in all populations studied. However, a significant increase in the APOE*2 allele frequency in the Mestizo (18.96%) and Negroid (16.25%) populations was found. Similar to results reported in other Native American populations we have found that the APOE*2 allele is completely absent in the Bari and Yucpa Amerindians. Frequencies found in the Colonia Tovar population are in agreement with those reported in the population of Germany, indicating a high degree of relatedness. The results support the notion that the distribution of the APOE alleles shows ethnic variability. Show more

Keywords: venezuelan populations, APOE, polymorphism

Citation: Disease Markers, vol. 21, no. 1, pp. 15-19, 2005

Authors: Pastorello, M.T. | Costa, R.S. | Ravinal, R.C. | Coimbra, M. | dos Reis, M.A | Dantas, M.

Article Type: Research Article

Abstract: Recent studies have demonstrated that α-Smooth Muscle actin expression in glomerular and tubulointerstitial compartments of renal tissue could represent a prognostic marker in several renal diseases. Our objective was to identify the prognostic value of α-SM actin actin expression on the evolution of renal damage in Primary IgA nephropathy (Berger's Disease). 43 patients followed up from 1988 to 1999 at the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil, was …studied. Clinical-laboratory data were obtained from the medical records of the patients using a protocol containing name, race, gender, origin, profession, age at clinical presentation of the disease and personal and family history. The parameters assessed in the approach to IgA nephropathy were serum creatinine, creatinine clearance, serum albumin, total serum protein, 24 hours proteinuria, glycaemia, serum sodium, potassium, calcium and phosphorus ions, analysis of urinary sediment, serum complement profile, blood count, and renal biopsy. Morphological evaluation was performed by renal biopsy using common light and immunofluorescence microscopy. Immunohistochemical studies were performed using a murine monoclonal antibody to α-SM actin. Our data showed that α-SM actin expression in the glomerular and tubulointerstitial compartments are not correlated with unfavorable clinical course of primary IgA nephropathy. Show more

Keywords: Berger's disease, primary IgA nephropathy, glomerulonephritis, hematuria, α-SM actin, prognostic factors, chronic renal progression

Citation: Disease Markers, vol. 21, no. 1, pp. 21-27, 2005

Authors: Frost, Petter | Jugessur, Astanand | Apold, Jaran | Heimdal, Ketil | Aloysius, Thomas | Eliassen, Aud K. | Fauske, Lars | Matre, Guri | Eiken, Hans Geir

Article Type: Research Article

Abstract: Mutations in the Breast-Cancer-1 (BRCA1) gene are the major cause of familial breast/ovarian cancer. Among familial breast cancer only, 15–20% have been suggested to have a deleterious mutation in BRCA1. A highly sensitive method (REF-SSCP) was applied to screen the open reading frame and the 5'UTRs of BRCA1 for mutations. The patient cohort comprised 61 unrelated moderate to high risk breast cancer patients from Western-Norway. Only one known deleterious BRCA1 mutation (c.816-817delGT) was found …in two of the 61 patients (3.3%). Four haplotypes were established based on nine known single nucleotide polymorphisms. Two patients had a novel deletion (c.-33_-29delAAAAA) in the 5'UTR, and a novel amino acid substitution (L523W) was found in one patient. Size variations analysis in the 5'UTR was repeated in a cohort of 159 unrelated familial breast/ovarian cancer patients and 94 healthy blood donors. Two patients were identified with 5'UTR (c.-30 to -60) variations (CAAAA)_5 and (CAAAA)_7 , instead of the (CAAAA)_6 -repeat. All of the identified 5'UTR size variations were localized between the start codon and the most stable secondary structures previously proposed for the exon 1b transcript. No such alterations were found among the healthy blood donors but association studies of the 5'UTR variations within the respective families were not conclusive. Show more

Keywords: familial cancer, breast cancer only, BRCA1, 5'UTR, genetic screening, haplotypes

Citation: Disease Markers, vol. 21, no. 1, pp. 29-36, 2005

Authors: Li, He Cheng | Cai, Qiu Yin | Shinohara, Eric T. | Cai, Hui | Cao, Carolyn | Fei Wang, Zuo | Teng, Ming | Zheng, Wei | Lu, Bo

Article Type: Research Article

Abstract: Endostatin is an important inhibitory molecule which mediates the sequential steps involved in angiogenesis. Lower level or impaired function of endostatin is associated with a higher risk of developing malignant solid tumors and with a worse prognosis of the disease. The endostatin N104 polymorphism might be associated with an impaired ability to inhibit angiogenesis. We analyzed the tissues from 98 Caucasian prostate cancer patients for the presence of D104N polymorphism. The frequencies of homozygous …4349G/G(104D/D), and heterozygous 4349G/A(104D/N) were 83.67%(82/98) and 16.33%(16/98), respectively; no individuals were homozygous 4349A/A(104N/N). With the Fisher's exact test we found the genotype of D104N was not significantly related to age, tumor grade, PSA and clinical stage (P > 0.05). There was no difference in relapse free survival(RFS) or overall survival(OS) between patients with 104D/N and those with 104D/D (P = 0.8283, 0.3713 respectively). We concluded that endostatin polymorphism was not associated with the aggressiveness of prostate cancer in Caucasian patients. Show more

Keywords: prostate cancer, endostatin, polymorphism

Citation: Disease Markers, vol. 21, no. 1, pp. 37-41, 2005

Authors: Kelly, Danny J. | Ghosh, Sujoy

Article Type: Research Article

Abstract: We have compared microarray data generated on Affymetrix™ chips from standard (8 micrograms) or low (100 nanograms) amounts of total RNA. We evaluated the gene signals and gene fold-change estimates obtained from the two methods and validated a subset of the results by real time, polymerase chain reaction assays. The correlation of low RNA derived gene signals to gene signals obtained from standard RNA was poor for less to moderately abundant genes. Genes with high abundance …showed better correlation in signals between the two methods. The signal correlation between the low RNA and standard RNA methods was improved by including a reference sample in the microarray analysis. In contrast, the fold-change estimates for genes were better correlated between the two methods regardless of the magnitude of gene signals. A reference sample based method is suggested for studies that would end up comparing gene signal data from a combination of low and standard RNA templates; no such referencing appears to be necessary when comparing fold-changes of gene expression between standard and low template reactions. Show more

Keywords: data comparability, submicrogram RNA, low template amplification, reference sample, gene expression

Citation: Disease Markers, vol. 21, no. 1, pp. 43-48, 2005