Abstract | BACKGROUND: 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:
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Authors | Márta Vitai, Szabolcs Fátrai, Péter Rass, Melinda Csordás, Ildikó Tarnai |
Journal | Clinical chemistry and laboratory medicine
(Clin Chem Lab Med)
Vol. 43
Issue 12
Pg. 1346-50
( 2005)
ISSN: 1434-6621 [Print] Germany |
PMID | 16309371
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Acatalasia
(blood, genetics)
- Aged
- Amino Acid Substitution
- Catalase
(blood, genetics)
- DNA Mutational Analysis
- Diabetes Mellitus, Type 2
(genetics)
- Exons
(genetics)
- Female
- Heme
(metabolism)
- Humans
- Hungary
- Introns
(genetics)
- Male
- Mass Screening
(methods)
- Middle Aged
- Mutation
- Oxidative Stress
- Polymerase Chain Reaction
(methods)
- Polymorphism, Single-Stranded Conformational
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