TY - JOUR AU - Nyesténé Nagy, Teréz AU - Paszti, Erika AU - Káplár, Miklós AU - Bhattoa Harjit, Pál AU - Góth, László TI - Further acatalasemia mutations in human patients from Hungary with diabetes and microcytic anemia JF - MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS J2 - MUTAT RES-FUND MOL M VL - 772 PY - 2015 SP - 10 EP - 14 PG - 5 SN - 0027-5107 DO - 10.1016/j.mrfmmm.2014.12.008 UR - https://m2.mtmt.hu/api/publication/2817325 ID - 2817325 N1 - Admin megjegyzés-24606632 AB - Abstract In blood, the hydrogen peroxide concentration is regulated by catalase. Decreased activity of catalase may lead to increased hydrogen peroxide concentration, which may contribute to the manifestation of age-related disease. The aim of this study is to examine association of decreased blood catalase activity and catalase exon mutations in patients (n = 617) with diabetes (n = 380), microcytic anemia (n = 58), beta-thalassemia (n = 43) and presbycusis (n = 136) and in controls (n = 295). Overall, 51 patients (8.3%) had less than half of normal blood catalase activity. Their genomic DNA was used for mutation screening of all exons and exon/intron boundaries with polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and PCR-heteroduplex analyses, and mutations were verified with nucleotide sequencing. Seven patients (type 2 diabetes (n = 3), gestational diabetes (n = 1), microcytic anemia (n = 2)) had four novel catalase exon mutations namely, c.106_107insC, p.G36Afs*5(n = 3, Hungarian type G1), c.379C>T, p.R127Y (n = 2, Hungarian type H1), c.390T>C, p.R129L, (n = 1, Hungarian type H2) and c.431A>T, p.N143V (n = 1, Hungarian type H3). In patients with decreased blood catalase, the incidence of acatalasemia mutations was significantly high (P < 0.0002) in microcytic anemia, type 2 and gestational diabetes. The four novel mutations were probably responsible for low blood catalase activity in 7/51 patients. In the remainder of the cases, other polymorphisms and epigenetic/regulatory factors may be involved. LA - English DB - MTMT ER - TY - JOUR AU - Nyesténé Nagy, Teréz AU - Csordás, M AU - Kósa, Z AU - Góth, László TI - A simple method for examination of polymorphisms of catalase exon 9: Rs769217 in Hungarian microcytic anemia and beta-thalassemia patients JF - ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS J2 - ARCH BIOCHEM BIOPHYS VL - 525 PY - 2012 IS - 2 SP - 201 EP - 206 PG - 6 SN - 0003-9861 DO - 10.1016/j.abb.2012.01.004 UR - https://m2.mtmt.hu/api/publication/2393863 ID - 2393863 N1 - N1 Molecular Sequence Numbers: GENBANK: NM_001752; Megjegyzés-23292847 N1 Molecular Sequence Numbers: GENBANK: NM_001752; Megjegyzés-23293008 N1 Molecular Sequence Numbers: GENBANK: NM_001752; Megjegyzés-23294270 N1 Molecular Sequence Numbers: GENBANK: NM_001752; Megjegyzés-24635651 N1 Molecular Sequence Numbers: GENBANK: NM_001752; Megjegyzés-24668585 N1 Molecular Sequence Numbers: GENBANK: NM_001752; Megjegyzés-23294621 N1 Molecular Sequence Numbers: GENBANK: NM_001752; AB - Catalase decreases the high, toxic concentrations of hydrogen peroxide but it lets the physiological, low concentrations in the cells mainly for signaling purposes. Its decreased activity may contribute to development of several pathological conditions. Catalase mutations occur frequently in exon 9, these were examined with different, complicated and costly methods. The aim of the current study was to evaluate a method for screening of polymorphisms in catalase exon 9. We used the slab gel electrophoresis of PCR amplicons without denaturation and silver staining for visualization of the DNA bands. We detected extra DNA bands in the 400-800 bp region of the catalase exon 9. Their single stranded nature was proved with nucleotide sequence analyses, comparison with the standard SSCP, staining with Sybr Green II and Sybr Green I, ethidium bromide, no digestion with RFLP (BstX I), and digestion with plant nuclease. We used this method for examination of polymorphisms of catalase exon 9 in microcytic anemia and beta-thalassemia patients. The lowest blood catalase activities were detected in microcytic anemia and beta-thalassemia patients with the TT genotypes of the C111T polymorphism. This method was sensitive for detection of G113A acatalasemia mutation, but poorly detected C37T and G5A acatalasemia mutations. © 2012 Elsevier Inc. All rights reserved. LA - English DB - MTMT ER - TY - JOUR AU - Góth, László AU - Vitai, Márta AU - Rass, P AU - Sükei, E AU - Páy, Anikó TI - Detection of a novel familial catalase mutation (Hungarian type D) and possible risk of inherited catalase deficiency for diabetes mellitus JF - ELECTROPHORESIS J2 - ELECTROPHORESIS VL - 26 PY - 2005 IS - 9 SP - 1646 EP - 1649 PG - 4 SN - 0173-0835 DO - 10.1002/elps.200410384 UR - https://m2.mtmt.hu/api/publication/1993025 ID - 1993025 AB - The enzyme catalase is the main regulator of hydrogen peroxide metabolism. Recentfindings suggest that a low concentration of hydrogen peroxide may act as a messengerin some signalling pathways whereas high concentrations are toxic for many cells and cell components. Acatalasemia is a genetically heterogeneous condition with a worldwide distribution. Yet only two Japanese and three Hungarian syndromecausing mutations have been reported. A large-scale (23 130 subjects) catalase screening program in Hungary yielded 12 hypocatalasemic families. The V family with four hypocatalasemics (60.667.6MU/L) and six normocatalasemic (103.6623.5MU/L)members was examined to define the mutation causing the syndrome. Mutation screening yielded four novel polymorphisms. Of these, three intron sequence variations, namely G?A at the nucleotide 60 position in intron 1, T?A atposition 11 in intron 2, and G?Tat position 31 in intron 12, are unlikely to be responsible for the decreased blood catalase activity. However, the novel G?A mutation in exon 9 changes the essential amino acid Arg 354 to Cys 354 and may indeed be responsible for the decreased catalase activity. This inherited catalase deficiency, by inducing an increased hydrogen peroxide steady-state concentration in vivo, may be involved in the early manifestation of type 2 diabetes mellitus for the 35-year old proband. LA - English DB - MTMT ER - TY - JOUR AU - Vitai, Márta AU - Fatrai, S AU - Rass, P AU - Csordas, M AU - Tarnai, I TI - Simple PCR heteroduplex, SSCP mutation screening methods for the detection of novel catalase mutations in Hungarian patients with type 2 diabetes mellitus JF - CLINICAL CHEMISTRY AND LABORATORY MEDICINE J2 - CLIN CHEM LAB MED VL - 43 PY - 2005 IS - 12 SP - 1346 EP - 1350 PG - 5 SN - 1434-6621 DO - 10.1515/CCLM.2005.230 UR - https://m2.mtmt.hu/api/publication/2539241 ID - 2539241 AB - Background: The enzyme catalase is the main regulator of hydrogen peroxide metabolism. Deficiency of catalase may cause high concentrations of hydrogen peroxide and increase the risk of the development of pathologies for which oxidative stress is a contributing factor, for example, type 2 diabetes mellitus. Catalase deficiency has been reported to be associated with increased frequency of diabetes mellitus in a cohort of patients in Hungary. In this cohort, the majority of mutations in the catalase gene occur in exon 2. Methods: Type 2 diabetic patients (n = 308) were evaluated for mutations in intron 1 (81 bp), exon 2 (172 bp) and intron 2 (13 bp) of the catalase gene. Screening for mutations utilized PCR single-strand conformational polymorphism (SSCP) and PCR heteroduplex methods. Verification of detected mutations was by nucleotide sequence analysis. Results: A total of 11 catalase gene mutations were detected in the 308 subjects (3.57%, p < 0.001). Five of the 11 were at two previously reported mutation sites: exon 2 (79) G insertion and (138) GA insertion. Six of the 11 were at five previously unreported catalase mutation sites: intron 1 (60) G -> T; intron 2 (7) G -> A and (5) G -> C; exon 2 (96) T -> A; and exon 2 (135) T -> A. The novel missense mutations on exon 2 (96 and 135) are associated with 59% and 48% decreased catalase activity, respectively; the novel G -> C mutation on intron 2 (5) is associated with a 62% decrease in catalase activity. Mutations detected on intron 1 (60) and intron 2 (7) showed no change in catalase activity. The G -> C mutation on intron 2 (5) might be a splicing mutation. The two missense mutations on exon 2 (96) and (135) cause substitutions of amino acids 53 (Asp -> Glu) and 66 (Glu -> Cys) of the catalase protein. These are close to amino acids that are important for the binding of heme to catalase, 44 (Val) and 72-75 Arg, Val, Val, His). Changes in heme binding may be responsible for the activity losses. Conclusion: Mutations that cause decreased catalase activity may contribute to susceptibility to inherited type 2 diabetes mellitus. Exon 2 and neighboring introns of the catalase gene may be minor hot spots for type 2 diabetes mellitus susceptibility mutations. LA - English DB - MTMT ER - TY - JOUR AU - Barja, G TI - Aging in vertebrates, and the effect of caloric restriction: a mitochondrial free radical production-DNA damage mechanism? JF - BIOLOGICAL REVIEWS J2 - BIOL REV VL - 79 PY - 2004 IS - 2 SP - 235 EP - 251 PG - 17 SN - 1464-7931 DO - 10.1017/S1464793103006213 UR - https://m2.mtmt.hu/api/publication/25464008 ID - 25464008 N1 - Cited By :191 Export Date: 21 March 2024 CODEN: BRCPA Correspondence Address: Barja, G.; Department of Animal Biology-II, , Madrid 28040, Spain LA - English DB - MTMT ER - TY - JOUR AU - Góth, László AU - Rass, P AU - Páy, Anikó TI - Catalase enzyme mutations and their association with diseases JF - MOLECULAR DIAGNOSIS J2 - MOL DIAGN VL - 8 PY - 2004 IS - 3 SP - 141 EP - 149 PG - 9 SN - 1084-8592 DO - 10.2165/00066982-200408030-00001 UR - https://m2.mtmt.hu/api/publication/2506535 ID - 2506535 N1 - Dept. of Clin. Analytical Chemistry, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary Dept. Clin. Biochem./Molec. Pathol., Medical and Health Science Center, University of Debrecen, Debrecen, Hungary Sigma-Aldrich Ltd., Budapest, Hungary Biological Research Center, Hungarian Academy of Science, Szeged, Hungary Dept. Clin. Biochem./Molec. Pathol., Medical and Health Science Center, University of Debrecen, PO Box 40, H-4012 Debrecen, Hungary Cited By :121 Export Date: 5 October 2020 CODEN: MDIAF Correspondence Address: Góth, L.; Dept. Clin. Biochem./Molec. Pathol., Medical and Health Science Center, University of Debrecen, PO Box 40, H-4012 Debrecen, Hungary; email: goth@dote.hu AB - Enzyme catalase seems to be the main regulator of hydrogen peroxide metabolism. Hydrogen peroxide at high concentrations is a toxic agent, while at low concentrations it appears to modulate some physiological processes such as signaling in cell proliferation, apoptosis, carbohydrate metabolism, and platelet activation. Benign catalase gene mutations of 5′ noncoding region (15) and intron 1 (4) have no effect on catalase activity and are not associated with disease. Catalase gene mutations have been detected in association with diabetes mellitus, hypertension, and vitiligo. Decreases in catalase activity in patients with tumors is more likely to be due to decreased enzyme synthesis rather than to catalase mutations. Acatalasemia, the inherited deficiency of catalase has been detected in 11 countries. Its clinical features might be oral gangrene, altered lipid, carbohydrate, homocysteine metabolism and the increased risk of diabetes mellitus. The Japanese, Swiss, and Hungarian types of acatalasemia display differences in biochemical and genetic aspects. However, there are only limited reports on the syndrome causing these mutations. These data show that acatalasemia may be a syndrome with clinical, biochemical, genetic characteristics rather than just a simple enzyme deficiency. © 2004 Adis Data Information BV. All rights reserved. LA - English DB - MTMT ER - TY - JOUR AU - Forsberg, L AU - de Faire, U AU - Morgenstern, R TI - Oxidative stress, human genetic variation, and disease JF - ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS J2 - ARCH BIOCHEM BIOPHYS VL - 389 PY - 2001 SP - 84 EP - 93 PG - 10 SN - 0003-9861 DO - 10.1006/abbi.2001.2295 UR - https://m2.mtmt.hu/api/publication/22160969 ID - 22160969 DB - MTMT ER - TY - JOUR AU - Góth, László TI - A new type of inherited catalase deficiencies: Its characterization and comparison to the Japanese and Swiss type of acatalasemia JF - BLOOD CELLS MOLECULES AND DISEASES J2 - BLOOD CELL MOL DIS VL - 27 PY - 2001 IS - 2 SP - 512 EP - 517 PG - 6 SN - 1079-9796 DO - 10.1006/bcmd.2001.0415 UR - https://m2.mtmt.hu/api/publication/2393883 ID - 2393883 N1 - Admin megjegyzés-24636722 #JournalID1# Name: Blood Cells, Molecules, and Diseases ISSN: 1079-9796 #JournalID2# Admin megjegyzés-24668524 #JournalID1# Name: Blood Cells, Molecules, and Diseases ISSN: 1079-9796 #JournalID2# Admin megjegyzés-24668604 #JournalID1# Name: Blood Cells, Molecules, and Diseases ISSN: 1079-9796 #JournalID2# Admin megjegyzés-24635670 #JournalID1# Name: Blood Cells, Molecules, and Diseases ISSN: 1079-9796 #JournalID2# AB - Thirteen Hungarian families that exhibited inherited catalase deficiencies have been detected. Differences between the deficiencies reported from Hungary and the previously reported Swiss acatalasemia were characterized using biochemical analysis of the catalase proteins. Molecular biological methods were used to compare the previously reported types of catalase deficiencies in Japan and the Hungarian deficiencies. Three mutations (a GA insertion in exon 2, a G insertion in exon 2, and a T to G substitution in intron 7) are responsible for decreased catalase activity in 7 of the 13 Hungarian kindreds; the other 6 families have not yet been characterized. These are not the mutations observed in Japan. Changes in lipid and carbohydrate metabolism and the high incidence (12.7%) of diabetes mellitus in the Hungarian kindreds suggest that individuals with inherited catalase deficiency are at risk of atherosclerosis and diabetes mellitus. The Hungarian subjects were detected during screening of a large population for catalase activity; no overt disease state was associated with the deficiencies. We hypothesize that the increased risk of disease may be due to prolonged exposure to elevated levels of blood hydrogen peroxide due to the lack of normal removal of hydrogen peroxide by blood catalase. © 2001 Academic Press. LA - English DB - MTMT ER - TY - JOUR AU - Góth, László TI - A novel catalase mutation (a G insertion in exon 2) causes the type B of the Hungarian acatalasemia JF - CLINICA CHIMICA ACTA J2 - CLIN CHIM ACTA VL - 311 PY - 2001 IS - 2 SP - 161 EP - 163 PG - 3 SN - 0009-8981 DO - 10.1016/S0009-8981(01)00609-X UR - https://m2.mtmt.hu/api/publication/2393882 ID - 2393882 LA - English DB - MTMT ER - TY - JOUR AU - Góth, László AU - Rass, P AU - Madarasi, I TI - A novel catalase mutation detected by polymerase chain reaction-single strand conformation polymorphism, nucleotide sequencing, and western blot analyses is responsible for the type C of Hungarian acatalasemia JF - ELECTROPHORESIS J2 - ELECTROPHORESIS VL - 22 PY - 2001 IS - 1 SP - 49 EP - 51 PG - 3 SN - 0173-0835 DO - 10.1002/1522-2683(200101)22:1<49::AID-ELPS49>3.0.CO;2-W UR - https://m2.mtmt.hu/api/publication/2875875 ID - 2875875 AB - Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) screening was used for searching mutations of the catalase gene in two Hungarian hypocatalasemic families. A syndrome-causing mutation was found in a PCR product containing exon 7 and its boundaries. Nucleotide sequence analyses detected a G to T substitution at position 5 of intron 7. The effect of this splice site mutation was confirmed by Western blot analyses demonstrating a decreased catalase protein level in these patients. These findings represent a novel type (C) of catalase mutations in the Hungarian acatalasemic/hypocatalasemic patients. LA - English DB - MTMT ER -